sibmedСибирский научный медицинский журналСибирский научный медицинский журнал2410-25122410-2520ИЦиГ СО РАН10.18699/SSMJ20260203sibmed-2820Research ArticleОБЗОРЫREVIEWSРоль врожденных лимфоидных клеток в патогенезе ревматических заболеванийThe role of innate lymphoid cells in the pathogenesis of rheumatic diseaseshttps://orcid.org/0000-0002-3975-0939ОвчинниковВ. С.OvchinnikovV. S.

Овчинников Виктор Сергеевич

630117, г. Новосибирск, ул. Арбузова, 6 

Viktor S. Ovchinnikov

630060, Novosibirsk, Arbuzova st., 6

Ovch.v.s@mail.ruhttps://orcid.org/0009-0000-4240-7878СевастьяновП. В.SevastyanovP. V.

Севастьянов Павел Васильевич

630117, г. Новосибирск, ул. Арбузова, 6 

Pavel V. Sevastyanov

630060, Novosibirsk, Arbuzova st., 6

p.sevastianov@alumni.nsu.ruhttps://orcid.org/0000-0003-2720-0961БоеваО. С.BoevaO. S.

Боева Ольга Сергеевна

630099, г. Новосибирск, ул. Ядринцевская, 14, корп. 201

Olga S. Boeva

630099, Novosibirsk, Yadrintsevskaya st., 14, block 201

starchenkova97@gmail.comhttps://orcid.org/0000-0002-4890-0847КоролевМ. А.KorolevM. A.

Королев Максим Александрович, д.м.н.

630117, г. Новосибирск, ул. Арбузова, 6 

Maksim A. Korolev, doctor of medical sciences

630060, Novosibirsk, Arbuzova st., 6

kormax@bk.ruНИИ клинической и экспериментальной лимфологии – филиал ФИЦ Институт цитологии и генетики СО РАНРоссияResearch Institute of Clinical and Experimental Lymphology – Branch of Institute of Cytology and Genetics of SB RASRussian FederationНИИ клинической и фундаментальной иммунологииРоссияResearch Institute of Clinical and Fundamental ImmunologyRussian Federation2026050520264622131Copyright © Овчинников В.С., Севастьянов П.В., Боева О.С., Королев М.А., 20262026Овчинников В.С., Севастьянов П.В., Боева О.С., Королев М.А.Ovchinnikov V.S., Sevastyanov P.V., Boeva O.S., Korolev M.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://sibmed.elpub.ru/jour/article/view/2820

Цель исследования – систематизировать современные данные о роли врожденных лимфоидных клеток (ILC) в патогенезе ревматических заболеваний, таких как ревматоидный артрит, псориатический артрит, аксиальный спондилоартрит, системный склероз и системная красная волчанка. Материал и методы. Проведен систематический обзор литературы из баз данных PubMed, Scopus и eLIBRARY.RU. Использовались ключевые слова: «врожденные лимфоидные клетки», «ILC», «ревматоидный артрит», «псориатический артрит», «спондилоартрит», «системный склероз», «системная красная волчанка». В обзоре представлена актуальная информация о роли различных субпопуляций ILC в патогенезе ревматических заболеваний, поддержании активности хронического воспаления в суставах и других органах-мишенях, участии ILC в регуляции патологического ремоделирования костной и хрящевой ткани, об их фенотипической и функциональной пластичности. Обсуждены перспективы терапевтического воздействия на ILC при помощи ингибиторов провоспалительных цитокинов и янус-киназы. Заключение. ILC играют важную роль в патогенезе ревматических заболеваний, таких как ревматоидный артрит, псориатический артрит, аксиальный спондилоартрит, системный склероз, системная красная волчанка. ILC регулируют воспаление и иммунный ответ, влияя на разрушение суставной ткани и остеокластогенез, при определенных условиях могут адаптироваться к изменениям микросреды, что открывает возможности для разработки таргетных терапевтических подходов. Применение препаратов, воздействующих на ILC, таких как ингибиторы сигнального пути JAK-STAT и антагонисты IL-17, показало обнадеживающие результаты, что делает перспективным разработку методов воздействия на данную субпопуляцию иммунных клеток. Однако необходимы дальнейшие исследования для более глубокого понимания механизмов действия ILC и совершенствования терапевтических подходов.

The aim of the study is to systematize current data on the role of innate lymphoid cells (ILC) in the pathogenesis of rheumatic diseases such as rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, systemic sclerosis, and systemic lupus erythematosus. Material and methods. A systematic review of the literature was conducted using data from PubMed, Scopus, and eLIBRARY.RU databases. The following keywords were used: «innate lymphoid cells», «ILC», «rheumatoid arthritis», «psoriatic arthritis», «spondyloarthritis», «systemic sclerosis», «systemic lupus erythematosus». This review presents up-to-date information on the role of various ILC subpopulations in the pathogenesis of rheumatic diseases, the maintenance of chronic inflammation in joints and other target organs, the involvement of ILC in the regulation of pathological remodeling of bone and cartilage tissue, as well as the phenotypic and functional plasticity of ILC. The perspectives of therapeutic modulation of ILC using inhibitors of pro-inflammatory cytokines and Janus kinases (JAK inhibitors) are discussed. Conclusions. ILC play a crucial role in the pathogenesis of rheumatological diseases such as rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, systemic sclerosis, and systemic lupus erythematosus. ILC regulate inflammation and the immune response, affecting joint tissue destruction and osteoclastogenesis. Under certain conditions, ILC can adapt to changes in the microenvironment, offering opportunities for the development of targeted therapeutic approaches. The use of drugs targeting ILC, such as JAK-STAT and IL-17 inhibitors, has shown encouraging results, making it a promising avenue for therapeutic interventions aimed at this immune cell subpopulation. However, further research is needed to deepen the understanding of ILC mechanisms and refine therapeutic strategies.

врожденные лимфоидные клеткиревматоидный артритпсориатический артритспондилоартритсистемный склерозсистемная красная волчанкаinnate lymphoid cellsrheumatoid arthritispsoriatic arthritisspondyloarthritissystemic sclerosissystemic lupus erythematosusРабота выполнена в рамках государственного задания НИИ клинической и экспериментальной лимфологии – филиала ФИЦ Институт цитологии и генетики СО РАН (тема FWNR-2025-0015)The work was carried out within the framework of the state task of the Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences (Project FWNR-2025-0015)ReferencesClottu A.S., Humbel M., Fluder N., Karampetsou M.P., Comte D. Innate lymphoid cells in autoimmune diseases. Front. Immunol. 2022;12:789788. doi: 10.3389/fimmu.2021.789788Clottu A.S., Humbel M., Fluder N., Karampetsou M.P., Comte D. Innate lymphoid cells in autoimmune diseases. Front. Immunol. 2022;12:789788. doi: 10.3389/fimmu.2021.789788Wang T., Rui J., Shan W., Xue F., Feng D., Dong L., Mao J., Shu Y., Mao C., Wang X. Imbalance of Th17, Treg, and helper innate lymphoid cell in the peripheral blood of patients with rheumatoid arthritis. Clin. Rheumatol. 2022;41:38373849. doi: 10.1007/s10067-022-06315-8Wang T., Rui J., Shan W., Xue F., Feng D., Dong L., Mao J., Shu Y., Mao C., Wang X. Imbalance of Th17, Treg, and helper innate lymphoid cell in the peripheral blood of patients with rheumatoid arthritis. Clin. Rheumatol. 2022;41:38373849. doi: 10.1007/s10067-022-06315-8de Pasquale C., Campana S., Bonaccorsi I., Carrega P., Ferlazzo G. Innate lymphoid cells in chronic inflammation, cancer and targeting with biologicals. Mol. Aspects Med. 2021;80:100963. doi: 10.1016/j.mam.2021.100963de Pasquale C., Campana S., Bonaccorsi I., Carrega P., Ferlazzo G. Innate lymphoid cells in chronic inflammation, cancer and targeting with biologicals. Mol. Aspects Med. 2021;80:100963. doi: 10.1016/j.mam.2021.100963Wu X. Innate lymphocytes in inflammatory arthritis. Front. Immunol. 2020;11:565275. doi: 10.3389/fimmu.2020.565275Wu X. Innate lymphocytes in inflammatory arthritis. Front. Immunol. 2020;11:565275. doi: 10.3389/fimmu.2020.565275Боева О.С., Козлов В.А., Сизиков А.Э., Королев М.А., Чумасова О.А., Омельченко В.О., Курочкина Ю.Д., Пашкина Е.А. Сравнение фенотипических свойств врожденных лимфоидных клеток на разных стадиях ревматоидного артрита. Мед. иммунол. 2023;25(5):1085–1090. doi: 10.15789/1563-0625-COP-2786Boeva O.S., Kozlov V.A., Sizikov A.E., Korolev M.A., Chumasova O.A., Omelchenko V.O., Kurochkina Yu.D., Pashkina E.A. Comparison of phenotypic properties of innate lymphoid cells at various stages of rheumatoid arthritis. Meditsinskaya immunologiya = Medical Immunology. 2023;25(5):10851090. [In Russian]. doi: 10.15789/1563-0625-COP-2786Omata Y., Frech M., Primbs T., Lucas S., Andreev D., Scholtysek C., Sarter K., Kindermann M., Yeremenko N., Baeten D.L., Andreas N., Kamradt T., Bozec A., Ramming A., Krönke G., Wirtz S., Schett G., Zaiss M.M. Group 2 innate lymphoid cells attenuate inflammatory arthritis and protect from bone destruction in mice. Cell Rep. 2018;24(1):169–180. doi: 10.1016/j.celrep.2018.06.005Omata Y., Frech M., Primbs T., Lucas S., Andreev D., Scholtysek C., Sarter K., Kindermann M., Yeremenko N., Baeten D.L., Andreas N., Kamradt T., Bozec A., Ramming A., Krönke G., Wirtz S., Schett G., Zaiss M.M. Group 2 innate lymphoid cells attenuate inflammatory arthritis and protect from bone destruction in mice. Cell Rep. 2018;24(1):169–180. doi: 10.1016/j.celrep.2018.06.005Боева О.С., Беришвили М.Т., Сизиков А.Э., Пашкина Е.А. Фенотипические особенности врожденных лимфоидных клеток при ревматоидном артрите. Рос. иммунол. ж. 2022;25(4):393–398. doi: 10.46235/1028-7221-1184-PFOBoeva O.S., Berishvili M.T., Sizikov A.E., Pashkina E.A. Phenotypic features of innate lymphoid cells in rheumatoid arthritis. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology. 2022;25(4):393–398. [In Russian]. doi: 10.46235/1028-7221-1184-PFOTakaki-Kuwahara A., Arinobu Y., Miyawaki K., Yamada H., Tsuzuki H., Irino K., Ayano M., Kimoto Y., Mitoma H., Akahoshi M., Tsukamoto H., Horiuchi T., Niiro H., Akashi K. CCR6+ Group 3 innate lymphoid cells accumulate in inflamed joints in rheumatoid arthritis and produce Th17 cytokines. Arthritis Res. Ther. 2019;21:198. doi: 10.1186/s13075-019-1984-xTakaki-Kuwahara A., Arinobu Y., Miyawaki K., Yamada H., Tsuzuki H., Irino K., Ayano M., Kimoto Y., Mitoma H., Akahoshi M., Tsukamoto H., Horiuchi T., Niiro H., Akashi K. CCR6+ Group 3 innate lymphoid cells accumulate in inflamed joints in rheumatoid arthritis and produce Th17 cytokines. Arthritis Res. Ther. 2019;21:198. doi: 10.1186/s13075-019-1984-xRodríguez-Carrio J., Hähnlein J.S., Ramwadhdoebe T.H., Semmelink J.F., Choi I.Y., van Lienden K.P., Maas M., Gerlag D.M., Tak P.P., Geijtenbeek T.B.H., van Baarsen L.G.M. Brief report: Altered innate lymphoid cell subsets in human lymph node biopsy specimens obtained during the at-risk and earliest phases of rheumatoid arthritis. Arthritis Rheumatol. 2017;69(1):70–76. doi: 10.1002/art.39811Rodríguez-Carrio J., Hähnlein J.S., Ramwadhdoebe T.H., Semmelink J.F., Choi I.Y., van Lienden K.P., Maas M., Gerlag D.M., Tak P.P., Geijtenbe- ek T.B.H., van Baarsen L.G.M. Brief report: Altered innate lymphoid cell subsets in human lymph node biopsy specimens obtained during the at-risk and earliest phases of rheumatoid arthritis. Arthritis Rheumatol. 2017;69(1):70–76. doi: 10.1002/art.39811Saferding V., Blüml S. Innate immunity as the trigger of systemic autoimmune diseases. J. Autoimmun. 2019;102:102382. doi: 10.1016/j.jaut.2019.102382Saferding V., Blüml S. Innate immunity as the trigger of systemic autoimmune diseases. J. Autoimmun. 2019;102:102382. doi: 10.1016/j.jaut.2019.102382Абдушукурова К.Р., Шоимова О.Р. Иммунопатогенетические основы ревматоидного артрита: обзор литературы. Евраз. ж. мед. и ест. наук. 2024;4(4):58–70. doi: 10.5281/zenodo.10939619Abdushukurova K.R., Shoimova O.R. Foundations of immunopathogenesis of rheumatoid arthritis: Review of literature. Evraziyskiy zhurnal meditsinskikh i estestvennykh nauk = Eurasian Journal of Medical and Natural Sciences. 2024;4(4):58–70. [In Russian]. doi: 10.5281/zenodo.10939619Shikhagaie M.M., Germar K., Bal S.M., Romero R.X., Spits H. Innate lymphoid cells in autoimmunity: emerging regulators in rheumatic diseases. Nat. Rev. Rheumatol. 2017;13:164–173. doi: 10.1038/nrrheum.2016.218Shikhagaie M.M., Germar K., Bal S.M., Romero R.X., Spits H. Innate lymphoid cells in autoimmunity: emerging regulators in rheumatic diseases. Nat. Rev. Rheumatol. 2017;13:164–173. doi: 10.1038/nrrheum.2016.218Yang F., Luo X., Zhu W., Li J., Zheng Z., Zhu P. Dysregulation of innate lymphoid cells in patients with active rheumatoid arthritis and mice with collagen-induced arthritis. Mediators Inflamm. 2021;2021:1915068. doi: 10.1155/2021/1915068Yang F., Luo X., Zhu W., Li J., Zheng Z., Zhu P. Dysregulation of innate lymphoid cells in patients with active rheumatoid arthritis and mice with collagen-induced arthritis. Mediators Inflamm. 2021;2021:1915068. doi: 10.1155/2021/1915068Lo Pizzo M., la Barbera L., Rizzo C., Mohammadnezhad L., Camarda F., Ciccia F., Guggino G. JAKSTAT inhibition modifies the ILC1 immune response in patients with rheumatoid arthritis. Clin. Exp. Rheumatol. 2024;42:593–600. doi: 10.55563/clinexprheumatol/hhcnmtLo Pizzo M., la Barbera L., Rizzo C., Mohammadnezhad L., Camarda F., Ciccia F., Guggino G. JAKSTAT inhibition modifies the ILC1 immune response in patients with rheumatoid arthritis. Clin. Exp. Rheumatol. 2024;42:593–600. doi: 10.55563/clinexprheumatol/hhcnmtLeijten E.F.A., van Kempen T.S., Boes M., Michels-van Amelsfort J.M.R., Hijnen D., Hartgring S.A.Y., van Roon J.A.G., Wenink M.H., Radstake T.R.D.J. Brief report: enrichment of activated group 3 innate lymphoid cells in psoriatic arthritis synovial fluid. Arthritis Rheumatol. 2015;67(10):26732678. doi: 10.1002/art.39261Leijten E.F.A., van Kempen T.S., Boes M., Michels-van Amelsfort J.M.R., Hijnen D., Hartgring S.A.Y., van Roon J.A.G., Wenink M.H., Radstake T.R.D.J. Brief report: enrichment of activated group 3 innate lymphoid cells in psoriatic arthritis synovial fluid. Arthritis Rheumatol. 2015;67(10):26732678. doi: 10.1002/art.39261Polese B., Zhang H., Thurairajah B., King I.L. Innate lymphocytes in psoriasis. Front. Immunol. 2020;11:242. doi: 10.3389/fimmu.2020.00242Polese B., Zhang H., Thurairajah B., King I.L. Innate lymphocytes in psoriasis. Front. Immunol. 2020;11:242. doi: 10.3389/fimmu.2020.00242Boutet M.-A., Nerviani A., Gallo Afflitto G., Pitzalis C. Role of the IL-23/IL-17 axis in psoriasis and psoriatic arthritis: the clinical importance of its divergence in skin and joints. Int. J. Mol. Sci. 2018;19:530. doi: 10.3390/ijms19020530Boutet M.-A., Nerviani A., Gallo Afflitto G., Pitzalis C. Role of the IL-23/IL-17 axis in psoriasis and psoriatic arthritis: the clinical importance of its divergence in skin and joints. Int. J. Mol. Sci. 2018;19:530. doi: 10.3390/ijms19020530Raimondo M.G., Rauber S., Luber M., Rius Rigau A., Weber S., Anchang C.G., Agarwal R., Soare A., Sticherling M., Rech J., Kleyer A., Distler J., Schett G., Ramming A. Type 3 innate lymphoid cells are key drivers of psoriatic arthritis. Ann. Rheum. Dis. 2020. doi: 10.1136/annrheumdis-2020-eular.5570Raimondo M.G., Rauber S., Luber M., Rius Rigau A., Weber S., Anchang C.G., Agarwal R., Soare A., Sticherling M., Rech J., Kleyer A., Distler J., Schett G., Ramming A. Type 3 innate lymphoid cells are key drivers of psoriatic arthritis. Ann. Rheum. Dis. 2020. doi: 10.1136/annrheumdis-2020-eular.5570Bugaut H., Aractingi S. Major role of the IL17/23 axis in psoriasis supports the development of new targeted therapies. Front. Immunol. 2021;12:621956. doi: 10.3389/fimmu.2021.621956Bugaut H., Aractingi S. Major role of the IL17/23 axis in psoriasis supports the development of new targeted therapies. Front. Immunol. 2021;12:621956. doi: 10.3389/fimmu.2021.621956Azuaga A.B., Ramírez J., Cañete J.D. Psoriatic arthritis: Pathogenesis and targeted therapies. Int. J. Mol. Sci. 2023;24:4901. doi: 10.3390/ijms24054901Azuaga A.B., Ramírez J., Cañete J.D. Psoriatic arthritis: Pathogenesis and targeted therapies. Int. J. Mol. Sci. 2023;24:4901. doi: 10.3390/ijms24054901Soare A., Weber S., Maul L., Rauber S., Gheorghiu A.M., Houssni I., Kleyer A., Luber M., Rech J., Schett G., Distler J., Ramming A. Innate lymphoid cells correlate with disease activity and bone remodelling in psoriatic arthritis. Ann. Rheum. Dis. 2018;76:890–899. doi: 10.1136/annrheumdis-2018-eular.7177Soare A., Weber S., Maul L., Rauber S., Gheorghiu A.M., Houssni I., Kleyer A., Luber M., Rech J., Schett G., Distler J., Ramming A. Innate lymphoid cells correlate with disease activity and bone remodelling in psoriatic arthritis. Ann. Rheum. Dis. 2018;76:890–899. doi: 10.1136/annrheumdis-2018-eular.7177Al-Mossawi M.H., Chen L., Fang H., Ridley A., de Wit J., Yager N., Hammitzsch A., Pulyakhina I., Fairfax B.P., Simone D., Yi Y., Bandyopadhyay S., Doig K., Gundle R., Kendrick B., Powrie F., Knight J.C., Bowness P. Unique transcriptome signatures and GM-CSF expression in lymphocytes from patients with spondyloarthritis. Nat. Commun. 2017;8:1510. doi: 10.1038/s41467-017-01771-2Al-Mossawi M.H., Chen L., Fang H., Ridley A., de Wit J., Yager N., Hammitzsch A., Pulyakhina I., Fairfax B.P., Simone D., Yi Y., Bandyopadhyay S., Doig K., Gundle R., Kendrick B., Powrie F., Knight J.C., Bowness P. Unique transcriptome signatures and GM-CSF expression in lymphocytes from patients with spondyloarthritis. Nat. Commun. 2017;8:1510. doi: 10.1038/s41467-017-01771-2Kavanaugh A., Puig L., Gottlieb A.B., Ritchlin C., You Y., Li S., Song M., Randazzo B., Rahman P., McInnes I.B. Efficacy and safety of ustekinumab in psoriatic arthritis patients with peripheral arthritis and physician-reported spondylitis: post-hoc analyses from two phase III, multicentre, double-blind, placebo-controlled studies (Psummit-1/Psummit-2). Ann. Rheum. Dis. 2016;75(11):1984–1988. doi: 10.1136/annrheum-dis-2015-209068Kavanaugh A., Puig L., Gottlieb A.B., Ritchlin C., You Y., Li S., Song M., Randazzo B., Rahman P., McInnes I.B. Efficacy and safety of ustekinumab in psoriatic arthritis patients with peripheral arthritis and physician-reported spondylitis: post-hoc analyses from two phase III, multicentre, double-blind, placebo-controlled studies (Psummit-1/Psummit-2). Ann. Rheum. Dis. 2016;75(11):1984–1988. doi: 10.1136/annrheum-dis-2015-209068Leijten E.F.A., van Kempen T.S., Boes M., Michels-van Amelsfort J.M.R., Hijnen D., Hartgring S.A.Y., van Roon J.A.G., Wenink M.H., Radstake T.R.D.J. Brief report: Enrichment of activated group 3 innate lymphoid cells in psoriatic arthritis synovial fluid. Arthritis Rheumatol. 2015;67(10):2673-2678. doi: 10.1002/art.39261Leijten E.F.A., van Kempen T.S., Boes M., Michels-van Amelsfort J.M.R., Hijnen D., Hartgring S.A.Y., van Roon J.A.G., Wenink M.H., Radstake T.R.D.J. Brief report: Enrichment of activated group 3 innate lymphoid cells in psoriatic arthritis synovial fluid. Arthritis Rheumatol. 2015;67(10):2673-2678. doi: 10.1002/art.39261Savage L.J., Wittmann M., McGonagle D., Helliwell P.S. Ustekinumab in the treatment of psoriasis and psoriatic arthritis. Rheumatol. Ther. 2015;2:1–16. doi: 10.1007/s40744-015-0010-2Savage L.J., Wittmann M., McGonagle D., Helliwell P.S. Ustekinumab in the treatment of psoriasis and psoriatic arthritis. Rheumatol. Ther. 2015;2:1–16. doi: 10.1007/s40744-015-0010-2Kavanaugh A., Ritchlin C., Rahman P., Puig L., Gottlieb A.B., Li S., Wang Y., Noonan L., Brodmerkel C., Song M., Mendelsohn A.M., McInnes I.B.; PSUMMIT-1 and 2 Study Groups. Ustekinumab, an anti-IL-12/23 p40 monoclonal antibody, inhibits radiographic progression in patients with active psoriatic arthritis: results of an integrated analysis of radiographic data from the phase 3, multicentre, randomised, double-blind, placebo-controlled PSUMMIT-1 and PSUMMIT-2 trials. Ann. Rheum. Dis. 2014;73:1000–1006. doi: 10.1136/annrheumdis-2013-204741Kavanaugh A., Ritchlin C., Rahman P., Puig L., Gottlieb A.B., Li S., Wang Y., Noonan L., Brodmerkel C., Song M., Mendelsohn A.M., McInnes I.B.; PSUMMIT-1 and 2 Study Groups. Ustekinumab, an anti-IL-12/23 p40 monoclonal antibody, inhibits radiographic progression in patients with active psoriatic arthritis: results of an integrated analysis of radiographic data from the phase 3, multicentre, randomised, double-blind, placebo-controlled PSUMMIT-1 and PSUMMIT-2 trials. Ann. Rheum. Dis. 2014;73:1000–1006. doi: 10.1136/annrheumdis-2013-204741Langley R.G., Lebwohl M., Krueger G.G., Szapary P.O., Wasfi Y., Chan D., Hsu M.C., You Y., Poulin Y., Korman N., Prinz J.C., Reich K.; on behalf of the PHOENIX 2 Investigators. Long-term efficacy and safety of ustekinumab, with and without dosing adjustment, in patients with moderate-to-severe psoriasis: results from the PHOENIX 2 study through 5 years of follow-up. Br. J. Dermatol.2015;172(5):1371–1383. doi: 10.1111/bjd.13469Langley R.G., Lebwohl M., Krueger G.G., Szapary P.O., Wasfi Y., Chan D., Hsu M.C., You Y., Poulin Y., Korman N., Prinz J.C., Reich K.; on behalf of the PHOENIX 2 Investigators. Long-term efficacy and safety of ustekinumab, with and without dosing adjustment, in patients with moderate-to-severe psoriasis: results from the PHOENIX 2 study through 5 years of follow-up. Br. J. Dermatol.2015;172(5):1371–1383. doi: 10.1111/bjd.13469Greven D.E.A., Cohen E.S., Gerlag D.M., Campbell J., Woods J., Davis N., van Nieuwenhuijze A., Lewis A., Heasmen S., McCourt M., Corkill D., Dodd A., Elvin J., Statache G., Wicks I.P., Anderson I.K., Nash A., Sleeman M.A., Tak P.P. Preclinical characterisation of the GM-CSF receptor as a therapeutic target in rheumatoid arthritis. Ann. Rheum. Dis. 2015;74(10):1924–1930. doi: 10.1136/annrheum-dis-2014-205234Greven D.E.A., Cohen E.S., Gerlag D.M., Campbell J., Woods J., Davis N., van Nieuwenhuijze A., Lewis A., Heasmen S., McCourt M., Corkill D., Dodd A., Elvin J., Statache G., Wicks I.P., Anderson I.K., Nash A., Sleeman M.A., Tak P.P. Preclinical characterisation of the GM-CSF receptor as a therapeutic target in rheumatoid arthritis. Ann. Rheum. Dis. 2015;74(10):1924–1930. doi: 10.1136/annrheum-dis-2014-205234Yeremenko N., Noordenbos T., Blijdorp I., Hreggvidsdottir H., Germar K., Bernink J.H., Spits H., Baeten D. Human type 1 innate lymphoid cells accumulatein the inflamed synovium in spondyloarthritis. Ann. Rheum. Dis. 2015. doi: 10.1136/annrheumdis-2015-eular.5907Yeremenko N., Noordenbos T., Blijdorp I., Hreggvidsdottir H., Germar K., Bernink J.H., Spits H., Baeten D. Human type 1 innate lymphoid cells accumulatein the inflamed synovium in spondyloarthritis. Ann. Rheum. Dis. 2015. doi: 10.1136/annrheumdis-2015-eular.5907Min H.K., Moon J., Lee S.-Y., Lee A.R., Lee C.R., Lee J., Kwok S.-K., Cho M.-L., Park S.-H. Expanded IL-22+ group 3 innate lymphoid cells and role of oxidized LDL-C in the pathogenesis of axial spondyloarthritis with dyslipidaemia.Immune Netw. 2021;21(6):e43. doi: 10.4110/in.2021.21.e43Min H.K., Moon J., Lee S.-Y., Lee A.R., Lee C.R., Lee J., Kwok S.-K., Cho M.-L., Park S.-H. Expanded IL-22+ group 3 innate lymphoid cells and role of oxidized LDL-C in the pathogenesis of axial spondyloarthritis with dyslipidaemia.Immune Netw. 2021;21(6):e43. doi: 10.4110/in.2021.21.e43Ciccia F., Guggino G., Zeng M., Thomas R., Ranganathan V., Rahman A., Alessandro R., Rizzo A., Saieva L., Macaluso F., Peralta S., Di Liberto D., Dieli F., Cipriani P., Giacomelli R., Baeten D., Haroon N. Proinflammatory CX3CR1+CD59+ tumor necrosis factor–like molecule 1A+ interleukin-23+ monocytes are expanded in patients with ankylosing spondylitis and modulate innate lymphoid cell 3 immune functions. Arthritis Rheumatol. 2018;70(12):2003–2013. doi: 10.1002/art.40582Ciccia F., Guggino G., Zeng M., Thomas R., Ranganathan V., Rahman A., Alessandro R., Rizzo A., Saieva L., Macaluso F., Peralta S., Di Liberto D., Dieli F., Cipriani P., Giacomelli R., Baeten D., Haroon N. Proinflammatory CX3CR1+CD59+ tumor necrosis factor–like molecule 1A+ interleukin-23+ monocytes are expanded in patients with ankylosing spondylitis and modulate innate lymphoid cell 3 immune functions. Arthritis Rheumatol. 2018;70(12):2003–2013. doi: 10.1002/art.40582Furst D.E., Louie J.S. Targeting inflammatory pathways in axial spondyloarthritis. Arthritis Res. Ther. 2019;21:188. doi: 10.1186/s13075-019-1885-zFurst D.E., Louie J.S. Targeting inflammatory pathways in axial spondyloarthritis. Arthritis Res. Ther. 2019;21:188. doi: 10.1186/s13075-019-1885-zWang R., Maksymowych W.P. Targeting the interleukin-23/interleukin-17 inflammatory pathway: successes and failures in the treatment of axial spondyloarthritis. Front. Immunol. 2021;12:715510. doi: 10.3389/fimmu.2021.715510Wang R., Maksymowych W.P. Targeting the interleukin-23/interleukin-17 inflammatory pathway: successes and failures in the treatment of axial spondyloarthritis. Front. Immunol. 2021;12:715510. doi: 10.3389/fimmu.2021.715510Mauro D., Macaluso F., Fasano S., Alessandro R., Ciccia F. ILC3 in axial spondyloarthritis: the gut angle. Curr. Rheumatol. Rep. 2019;21:37. doi: 10.1007/s11926-019-0834-9Mauro D., Macaluso F., Fasano S., Alessandro R., Ciccia F. ILC3 in axial spondyloarthritis: the gut angle. Curr. Rheumatol. Rep. 2019;21:37. doi: 10.1007/s11926-019-0834-9Liu Y., Shen Y., Ding H., He D., Cheng P., Wu X., Xiang Z., Shen L., Bian Y., Zhu Q. T-bet+ ILC3 in peripheral blood is increased in the ankylosing spondylitis with high disease activity. Heliyon. 2025;11:e41678. doi: 10.1016/j.heliyon.2025.e41678Liu Y., Shen Y., Ding H., He D., Cheng P., Wu X., Xiang Z., Shen L., Bian Y., Zhu Q. T-bet+ ILC3 in peripheral blood is increased in the ankylosing spondylitis with high disease activity. Heliyon. 2025;11:e41678. doi: 10.1016/j.heliyon.2025.e41678Cozzi G., Scagnellato L., Lorenzin M., Savarino E., Zingone F., Ometto F., Favero M., Doria A., Vavricka S.R., Ramonda R. Spondyloarthritis with inflammatory bowel disease: the latest on biologic and targeted therapies. Nat. Rev. Rheumatol. 2023;19:657671. doi: 10.1038/s41584-023-00984-8Cozzi G., Scagnellato L., Lorenzin M., Savarino E., Zingone F., Ometto F., Favero M., Doria A., Vavricka S.R., Ramonda R. Spondyloarthritis with inflammatory bowel disease: the latest on biologic and targeted therapies. Nat. Rev. Rheumatol. 2023;19:657671. doi: 10.1038/s41584-023-00984-8Pedersen S.J., Maksymowych W.P. Beyond the TNF-α inhibitors: new and emerging targeted therapies for patients with axial spondyloarthritis and their relation to pathophysiology. Drugs. 2018;78:1397–1418. doi: 10.1007/s40265-018-0971-xPedersen S.J., Maksymowych W.P. Beyond the TNF-α inhibitors: new and emerging targeted therapies for patients with axial spondyloarthritis and their relation to pathophysiology. Drugs. 2018;78:1397–1418. doi: 10.1007/s40265-018-0971-xWohlfahrt T., Usherenko S., Englbrecht M., Dees C., Weber S., Beyer C., Gelse K., Distler O., Schett G., Distler J.H., Ramming A. Type 2 innate lymphoid cell counts are increased in patients with systemic sclerosis and correlate with the extent of fibrosis. Ann. Rheum. Dis. 2016;75(3):623–626. doi: 10.1136/annrheumdis-2015-207388Wohlfahrt T., Usherenko S., Englbrecht M., Dees C., Weber S., Beyer C., Gelse K., Distler O., Schett G., Distler J.H., Ramming A. Type 2 innate lymphoid cell counts are increased in patients with systemic sclerosis and correlate with the extent of fibrosis. Ann. Rheum. Dis. 2016;75(3):623–626. doi: 10.1136/annrheumdis-2015-207388Roan F., Stoklasek T.A., Whalen E., Molitor J.A., Bluestone J.A., Buckner J.H., Ziegler S.F. Correction: CD4+ group 1 innate lymphoid cells (ILC) form a functionally distinct ILC subset that is increased in systemic sclerosis. J.Immunol. 2016;196(9):3966. doi: 10.4049/jimmunol.1600364Roan F., Stoklasek T.A., Whalen E., Molitor J.A., Bluestone J.A., Buckner J.H., Ziegler S.F. Correction: CD4+ group 1 innate lymphoid cells (ILC) form a functionally distinct ILC subset that is increased in systemic sclerosis. J.Immunol. 2016;196(9):3966. doi: 10.4049/jimmunol.1600364Laurent P., Allard B., Manicki P., Jolivel V., Levionnois E., Jeljeli M., Henrot P., Izotte J., Leleu D., Groppi A., Seneschal J., Constans J., Chizzolini C., Richez C., Duffau P., Lazaro E., Forcade E., Schaeverbeke T., Pradeu T., Batteux F., Blanco P., Contin-Bordes C., Truchetet M.-E. TGF-beta promotes low IL10-producing ILC2 with profibrotic ability involved in skin fibrosis in systemic sclerosis. Ann. Rheum. Dis. 2021;80(12):1594–1603. doi: 10.1136/annrheumdis-2020-219748Laurent P., Allard B., Manicki P., Jolivel V., Levionnois E., Jeljeli M., Henrot P., Izotte J., Leleu D., Groppi A., Seneschal J., Constans J., Chizzolini C., Richez C., Duffau P., Lazaro E., Forcade E., Schaeverbeke T., Pradeu T., Batteux F., Blanco P., Contin-Bordes C., Truchetet M.-E. TGF-beta promotes low IL10-producing ILC2 with profibrotic ability involved in skin fibrosis in systemic sclerosis. Ann. Rheum. Dis. 2021;80(12):1594–1603. doi: 10.1136/annrheumdis-2020-219748Wang L., Tang J., Yang X., Zanvit P., Cui K., Ku W.L., Jin W., Zhang D., Goldberg N., Cain A., Ni B., Zhao K., Wu Y., Chen W. TGF-beta induces ST2 and programs ILC2 development. Nat. Commun. 2020;11:35. doi: 10.1038/s41467-019-13734-wWang L., Tang J., Yang X., Zanvit P., Cui K., Ku W.L., Jin W., Zhang D., Goldberg N., Cain A., Ni B., Zhao K., Wu Y., Chen W. TGF-beta induces ST2 and programs ILC2 development. Nat. Commun. 2020;11:35. doi: 10.1038/s41467-019-13734-wGuo C., Zhou M., Zhao S., Huang Y., Wang S., Fu R., Li M., Zhang T., Gaskin F., Yang N., Fu S.M. Innate lymphoid cell disturbance with increase in ILC1 insystemic lupus erythematosus. Clin. Immunol. 2019;202:49–58. doi: 10.1016/j.clim.2019.03.008Guo C., Zhou M., Zhao S., Huang Y., Wang S., Fu R., Li M., Zhang T., Gaskin F., Yang N., Fu S.M. Innate lymphoid cell disturbance with increase in ILC1 insystemic lupus erythematosus. Clin. Immunol. 2019;202:49–58. doi: 10.1016/j.clim.2019.03.008Jiang Y., Zhao Y., Liu Y., Huang Q., Meng W., Xu H., Mo X. Imbalanced innate lymphoid cells are associated with disease activity and arthritis involvement in patients with systemic lupus erythematosus. Arch. Rheumatol. 2020;35(4):521–532. doi: 10.46497/ArchRheumatol.2020.7440Jiang Y., Zhao Y., Liu Y., Huang Q., Meng W., Xu H., Mo X. Imbalanced innate lymphoid cells are associated with disease activity and arthritis involvement in patients with systemic lupus erythematosus. Arch. Rheumatol. 2020;35(4):521–532. doi: 10.46497/ArchRheumatol.2020.7440Blokland S.L.M., van den Hoogen L.L., Leijten E.F.A., Hartgring S.A.Y., Fritsch R., Kruize A.A., van Roon J.A.G., Radstake T.R.D.J. Increased expression of Fas on group 2 and 3 innate lymphoid cells is associated with an interferon signature in systemic lupus erythematosus and Sjogren’s syndrome. Rheumatology (Oxford). 2019;58(10):1740–1745. doi: 10.1093/rheumatology/kez116Blokland S.L.M., van den Hoogen L.L., Leijten E.F.A., Hartgring S.A.Y., Fritsch R., Kruize A.A., van Roon J.A.G., Radstake T.R.D.J. Increased expression of Fas on group 2 and 3 innate lymphoid cells is associated with an interferon signature in systemic lupus erythematosus and Sjogren’s syndrome. RheumatologyHou M., Liu S. Innate lymphoid cells are increased in systemic lupus erythematosus. Clin. Exp. Rheumatol. 2019;37(4):676–679.(Oxford). 2019;58(10):1740–1745. doi: 10.1093/rheumatology/kez116Hou M., Liu S. Innate lymphoid cells are increased in systemic lupus erythematosus. Clin. Exp. Rheumatol. 2019;37(4):676–679.Hou M., Liu S. Innate lymphoid cells are increased in systemic lupus erythematosus. Clin. Exp. Rheumatol. 2019;37(4):676–679.

The authors declare that there are no conflicts of interest present.