Chronic Inflammation in Patients with Rheumatoid Arthritis or Spondyloarthritis Alters Regulatory T Cells Identity

Tessnime Abaab¹, Lyna Mebrek¹, Marie-Christophe Boissier², Luca Semerano³, Jerome Biton¹ and Natacha Bessis¹, ¹INSERM UMR 1125, Sorbonne Paris Nord University, Bobigny, France, ²INSERM UMR 1125, Sorbonne Paris Nord University,Rheumatology Dpt, APHP, GHUPSSD, Avicenne Hosp, Bobigny, France, ³Hopital Avicenne - AP-HP, Sorbonne Paris Nord University, INSERM UMR1125, Bobigny Cedex, France

Meeting: ACR Convergence 2022

Keywords: rheumatoid arthritis, spondyloarthritis, T Cell, Treg cells

Session Information

Date: Monday, November 14, 2022

Title: T Cell Biology and Targets in Autoimmune and Inflammatory Disease Poster

Session Type: Poster Session D

Session Time: 1:00PM-3:00PM

Background/Purpose: Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are inflammatory autoimmune diseases associated with impaired regulatory T cell (Tregs) function. Tregs identity varies according to their microenvironment. Under inflammatory conditions, their stability may be altered, which may lead to a decrease in their suppressive activity. In the present work, we evaluated Tregs stability in patients with RA and SpA.

Methods: Expression of epigenetic or transcriptional regulators (EZH2¹, Helios, pSTAT5) known to stabilize FoxP3, and suppressive markers (TNFR2, CD39) were evaluated on Tregs from blood of healthy donors (HD, n=17) and RA (n=27) or SpA (n = 32) patients free of targeted therapies. CPI-1205, an EZH2 inhibitor, was used to study the role of EZH2 in Treg differentiation and suppressive activity. Collagen-induced arthritis (CIA) was induced in mice treated or not with etanercept.

Results: The expression of the stability inducer EZH2, but not that of Helios, was decreased in Treg in both RA and SpA patients, as compared to HD. Interestingly, we revealed a link between the stability marker EZH2 and Treg suppressive markers, since EZH2 was preferentially expressed in TNFR2⁺ and CD39⁺ suppressive Treg sub-populations. Furthermore, we showed that functional inhibition of EZH2 attenuated in vitro Treg differentiation and suppressive function. Finally, we focused on another major Treg stability marker, phospho (p)STAT5⁺. Again, we showed that pSTAT5⁺ Tregs frequency was lower in RA and SpA patients than in HD. Moreover, in mice with CIA, a TNF inhibitor (etanercept) treatment increased Treg stability, at least in part, by restoring pSTAT5⁺ Treg frequency.

Conclusion: Altogether, these results highlighting the role of EZH2 and pSTAT5 on Treg functions, suggest that Treg stability is altered during chronic inflammation in RA and SpA patients. In the future, characterization of Treg stability markers deficiency in chronic inflammation could help to design efficient Treg cell-based therapies.

Disclosures: T. Abaab, None; L. Mebrek, None; M. Boissier, None; L. Semerano, None; J. Biton, None; N. Bessis, None.

To cite this abstract in AMA style:

Abaab T, Mebrek L, Boissier M, Semerano L, Biton J, Bessis N. Chronic Inflammation in Patients with Rheumatoid Arthritis or Spondyloarthritis Alters Regulatory T Cells Identity [abstract]. Arthritis Rheumatol. 2022; 74 (suppl 9). https://acrabstracts.org/abstract/chronic-inflammation-in-patients-with-rheumatoid-arthritis-or-spondyloarthritis-alters-regulatory-t-cells-identity/. Accessed .

« Back to ACR Convergence 2022

ACR Meeting Abstracts - https://acrabstracts.org/abstract/chronic-inflammation-in-patients-with-rheumatoid-arthritis-or-spondyloarthritis-alters-regulatory-t-cells-identity/