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A7.03 Il-33 inhibits experimental arthritis through CD25+ and CD25- regulatory T cells activation
  1. J Biton1,2,
  2. F Santinon1,
  3. D Lemeiter1,
  4. MC Boissier1,3,
  5. N Bessis1
  1. 1INSERM UMR 1125 Sorbonne Paris Cité, Université Paris 13, 74 Rue Marcel Cachin, 93000, Bobigny, France
  2. 2Present Address: INSERM UMRS 1138 Equipe 19, Centre de Recherche Des Cordeliers, F-75006, Paris, France
  3. 3Assistance Publique-Hôpitaux de Paris AP-HP, Hôpital Avicenne, Service de Rhumatologie, 125 Rue de Stalingrad, 93000, Bobigny, France

Abstract

Background and objectives Interleukin (IL)-33 is a new member of the IL-1 family that exerts pleiotropic activities in innate and  adaptive immunity. Some evidence also suggest that the IL-33/ST2 (IL-33 receptor) axis is strongly involved in the pathophysiology of rheumatoid arthritis (RA). We recently showed that IL-33 was able to inhibit collagen-induced arthritis (CIA) by promoting a regulatory T cell (Tregs) population overexpressing CD39 and ST2L. This work aimed at further enlightening the involvement of regulatory T cells in the IL-33-mediated effect in arthritis.

Results To further study the implication of Treg in IL-33 therapeutic effect, we evaluated IL-33 mediated effect in the absence of CD25+ Treg in CIA by co-administering IL-33 together with a depleting anti-CD25 antibody. As expected, this antibody obviously suppressed CD25 expressing CD4+FoxP3+ Treg population. In contrast, while CD4+FoxP3+CD25+ Treg were depleted, IL-33 dramatically amplified a population of CD25 negative CD4+FoxP3+ Treg in mice with CIA. We confirmed in an in vitro system this strong impact of IL-33 on CD25- Treg. On the contrary, IL-2 had no impact in vitro on this non-expressing CD25 cells.

Conclusion In absence of the alpha chain of the IL-2 receptor (CD25), IL-33 is still able to induce Treg expansion probably independently of IL-2 by a direct effect on ST2L-expressing Treg. Finally, this set of experiments reinforces the strong impact of IL-33 on both CD25+ and CD25- Treg subpopulations, therefore strengthening the involvement of these cells in the therapeutic effect of IL-33 in CIA.

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