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A8.30 Collagen-induced arthritis and imiquimod-induced psoriasis development is unaffected by the absence of interleukin-33
  1. S Khaleghparast Athari1,2,
  2. J Biton1,2,3,
  3. R Hervé1,2,
  4. A Raffaillac1,2,
  5. D Lemeiter1,2,
  6. A Herbelin4,
  7. L Semerano1,2,5,
  8. JP Girard6,
  9. F Caux1,2,7,
  10. MC Boissier1,2,5,
  11. N Bessis1,2
  1. 1 INSERM, U1125, F-93017, Bobigny, France
  2. 2 Sorbonne Paris Cité Université Paris 13, Bobigny, France
  3. 3 Present Address: INSERM UMRS 1138 Equipe 13, Centre de Recherche Des Cordeliers, Paris, France
  4. 4 INSERM U1082, Pôle Biologie Santé, BP 633, Poitiers, France
  5. 5 Assistance Publique-Hôpitaux de Paris, Avicenne Hospital, Rheumatology Department, Bobigny, France
  6. 6 Institut de Pharmacologie Et de Biologie Structurale (IPBS) CNRS-Université de Toulouse III, Toulouse, France
  7. 7 Assistance Publique-Hôpitaux de Paris, Avicenne Hospital, Dermatology Department, Bobigny, France


Background and objectives Interleukin (IL)-33 is a dual cytokine with both an alarmin role and a Th2-like inducing effect. It is involved in the pathogenesis of rheumatoid arthritis (RA) and its models, and we recently demonstrated that exogenous IL-33 was able to inhibit collagen-induced arthritis (CIA) in C57Bl/6 mice. However, its physiopathological role in RA is unclear. For instance, mice deficient for its receptor ST2 are more susceptible to arthritis, while the disease is not modified in IL-33 deficient mice. We aimed at studying the immune response in wild type mice and IL-33 deficient mice with CIA. To further understand the place of endogenous IL-33 in inflammatory diseases, we also studied its role in a model of skin inflammation.

Material and methods CIA was induced in IL-33-lacZ gene trap ( IL-33gt ) reporter strain mice (J Immunol, 2012, 188:3488; gift from JP Girard, Toulouse). These mice, generated on a C57BL/6 background, are deficient for IL-33 gene but express lacZ under the IL-33 promoter. IL-33 expression was analysed by X-Gal staining in various mice compartments. CD4+FoxP3+ regulatory T cells (Tregs), Th1 and Th17 frequencies were evaluated by flow cytometry in wt and IL-33gt mice. Bone resorption was studied by evaluating osteoclasts activity on a synthetic mineral matrix. Psoriasis-like skin inflammation was induced by immiquimod skin application.

Results We first confirmed that IL-33 gt mice develop CIA with similar severity than wild-type ( wt) littermates mice. IL-33 promotor activity was detected in the joints of IL-33 gt mice after CIA induction. Tregs, Th1 and Th17 frequencies were not modified in the spleen and lymph nodes of both strains. After CIA induction, osteoclast activity was higher in IL-33 gt mice than in wt mice, although differences were not significant. Interestingly, psoriasis development was not impaired in IL-33 gt mice.

Conclusions Despite its expression in the synovium of arthritic mice, IL-33 is not required for CIA development, any more than in psoriasis. Its absence also doesn’t influence T cell shift toward Th1, Th17 or Tregs sub-populations. Altogether, these data and our previous ones, showing that exogenous IL-33 can almost completely inhibit CIA development, suggest that this cytokine is not crucial for chronic inflammation development, but that the development of treatment based on IL-33/ST2 axis targeting should be considered.

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