The Th17 Pathway in Vascular Inflammation: Culprit or Consort?

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2022 Apr 28

PMID 35479069

Authors

Marie Robert

Pierre Miossec

Arnaud Hot

Affiliations

Soon will be listed here.

Abstract

The involvement of IL-17A in autoimmune and inflammatory diseases has prompted the development of therapeutic strategies to block the Th17 pathway. Promising results came from their use in psoriasis and in ankylosing spondylitis. IL-17A acts on various cell types and has both local and systemic effects. Considering the premature mortality observed during chronic inflammatory diseases, IL-17A action on vascular cells was studied. Both and results suggest that this cytokine favors inflammation, coagulation and thrombosis and promotes the occurrence of cardiovascular events. These observations led to study the role of IL-17A in diseases characterized by vascular inflammation, namely allograft rejection and vasculitis. Increased circulating levels of IL-17A and histological staining reveal that the Th17 pathway is involved in the pathogenesis of these diseases. Vasculitis treatment faces challenges while the use of steroids has many side effects. Regarding results obtained in giant cell arteritis with IL-6 inhibitors, a cytokine involved in Th17 differentiation, the use of anti-IL-17 is a promising strategy. However, lessons from rheumatoid arthritis and multiple sclerosis must be learnt before targeting IL-17 in vasculitis, which may be culprit, consort or both of them.

Citing Articles

Repair mechanisms of bone system tissues based on comprehensive perspective of multi-omics.

Yu H, Yang S, Jiang T, Li T, Duan H, Li M Cell Biol Toxicol. 2025; 41(1):45.

PMID: 39966216 PMC: 11836151. DOI: 10.1007/s10565-025-09995-5.

Vitamin D affects antiphospholipid syndrome by regulating T cells (Review).

Huo R, Yang Y, Wei C, Huo X, Meng D, Yang Y Int J Mol Med. 2024; 55(2).

PMID: 39670300 PMC: 11670861. DOI: 10.3892/ijmm.2024.5471.

Gut-derived immune cells and the gut-lung axis in ARDS.

Ziaka M, Exadaktylos A Crit Care. 2024; 28(1):220.

PMID: 38965622 PMC: 11225303. DOI: 10.1186/s13054-024-05006-x.

A Comprehensive Flow Cytometry Panel for Analysis of Idiopathic Subglottic Stenosis.

So R, Collins S, Chan-Li Y, Lina I, Gelbard A, Motz K Otolaryngol Head Neck Surg. 2024; 171(3):791-798.

PMID: 38606634 PMC: 11349474. DOI: 10.1002/ohn.754.

The IL-17 pathway as a target in giant cell arteritis.

Zeisbrich M, Thiel J, Venhoff N Front Immunol. 2024; 14:1199059.

PMID: 38299156 PMC: 10828953. DOI: 10.3389/fimmu.2023.1199059.

References

Hellmich B, Agueda A, Monti S, Buttgereit F, de Boysson H, Brouwer E . 2018 Update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2019; 79(1):19-30. DOI: 10.1136/annrheumdis-2019-215672. View

Noack M, Miossec P . Th17 and regulatory T cell balance in autoimmune and inflammatory diseases. Autoimmun Rev. 2014; 13(6):668-77. DOI: 10.1016/j.autrev.2013.12.004. View

Caplan A, Fett N, Rosenbach M, Werth V, Micheletti R . Prevention and management of glucocorticoid-induced side effects: A comprehensive review: A review of glucocorticoid pharmacology and bone health. J Am Acad Dermatol. 2016; 76(1):1-9. DOI: 10.1016/j.jaad.2016.01.062. View

Samson M, Ghesquiere T, Berthier S, Bonnotte B . Ustekinumab inhibits Th1 and Th17 polarisation in a patient with giant cell arteritis. Ann Rheum Dis. 2017; 77(2):e6. DOI: 10.1136/annrheumdis-2017-211622. View

Bilal J, Berlinberg A, Bhattacharjee S, Trost J, Riaz I, Kurtzman D . A systematic review and meta-analysis of the efficacy and safety of the interleukin (IL)-12/23 and IL-17 inhibitors ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab and tildrakizumab for the treatment of moderate to severe plaque.... J Dermatolog Treat. 2018; 29(6):569-578. DOI: 10.1080/09546634.2017.1422591. View

Faust S, Lu G, Marini B, Zou W, Gordon D, Iwakura Y . Role of T cell TGFbeta signaling and IL-17 in allograft acceptance and fibrosis associated with chronic rejection. J Immunol. 2009; 183(11):7297-306. PMC: 2819141. DOI: 10.4049/jimmunol.0902446. View

Shulman S, Rowley A . Kawasaki disease: insights into pathogenesis and approaches to treatment. Nat Rev Rheumatol. 2015; 11(8):475-82. DOI: 10.1038/nrrheum.2015.54. View

Leccese P, Alpsoy E . Behçet's Disease: An Overview of Etiopathogenesis. Front Immunol. 2019; 10:1067. PMC: 6523006. DOI: 10.3389/fimmu.2019.01067. View

Shimojima Y, Ishii W, Kishida D, Fukushima K, Ikeda S . Imbalanced expression of dysfunctional regulatory T cells and T-helper cells relates to immunopathogenesis in polyarteritis nodosa. Mod Rheumatol. 2016; 27(1):102-109. DOI: 10.3109/14397595.2016.1172999. View

10.

Abdulahad W, Stegeman C, Limburg P, Kallenberg C . Skewed distribution of Th17 lymphocytes in patients with Wegener's granulomatosis in remission. Arthritis Rheum. 2008; 58(7):2196-205. DOI: 10.1002/art.23557. View

11.

Coit P, De Lott L, Nan B, Elner V, Sawalha A . DNA methylation analysis of the temporal artery microenvironment in giant cell arteritis. Ann Rheum Dis. 2015; 75(6):1196-202. DOI: 10.1136/annrheumdis-2014-207116. View

12.

Rasouli M, Heidari B, Kalani M . Downregulation of Th17 cells and the related cytokines with treatment in Kawasaki disease. Immunol Lett. 2014; 162(1 Pt A):269-75. DOI: 10.1016/j.imlet.2014.09.017. View

13.

Comarmond C, Cacoub P . Granulomatosis with polyangiitis (Wegener): clinical aspects and treatment. Autoimmun Rev. 2014; 13(11):1121-5. DOI: 10.1016/j.autrev.2014.08.017. View

14.

Miossec P, Korn T, Kuchroo V . Interleukin-17 and type 17 helper T cells. N Engl J Med. 2009; 361(9):888-98. DOI: 10.1056/NEJMra0707449. View

15.

Savioli B, Abdulahad W, Brouwer E, Kallenberg C, de Souza A . Are cytokines and chemokines suitable biomarkers for Takayasu arteritis?. Autoimmun Rev. 2017; 16(10):1071-1078. DOI: 10.1016/j.autrev.2017.07.023. View

16.

Summers S, Steinmetz O, Gan P, Ooi J, Odobasic D, Kitching A . Toll-like receptor 2 induces Th17 myeloperoxidase autoimmunity while Toll-like receptor 9 drives Th1 autoimmunity in murine vasculitis. Arthritis Rheum. 2010; 63(4):1124-35. DOI: 10.1002/art.30208. View

17.

Samson M, Greigert H, Ciudad M, Gerard C, Ghesquiere T, Trad M . Improvement of Treg immune response after treatment with tocilizumab in giant cell arteritis. Clin Transl Immunology. 2021; 10(9):e1332. PMC: 8435365. DOI: 10.1002/cti2.1332. View

18.

Rani L, Minz R, Sharma A, Anand S, Gupta D, Panda N . Predominance of PR3 specific immune response and skewed TH17 vs. T-regulatory milieu in active granulomatosis with polyangiitis. Cytokine. 2014; 71(2):261-7. DOI: 10.1016/j.cyto.2014.10.005. View

19.

Miyabe C, Miyabe Y, Strle K, Kim N, Stone J, Luster A . An expanded population of pathogenic regulatory T cells in giant cell arteritis is abrogated by IL-6 blockade therapy. Ann Rheum Dis. 2016; 76(5):898-905. PMC: 5744591. DOI: 10.1136/annrheumdis-2016-210070. View

20.

Lin F, Jiang G, Shan J, Zhu C, Zou J, Wu X . Imbalance of regulatory T cells to Th17 cells in IgA nephropathy. Scand J Clin Lab Invest. 2012; 72(3):221-9. DOI: 10.3109/00365513.2011.652158. View