Active immunization against IL-23p19 improves experimental arthritis

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• 作者：Rojo Anthony  ; Ratsimandresy^a ;   ; ¹ ;   ; ^{rratsima@gmail.com} ; Emilie  ; Duvallet^b ;   ; ¹ ;   ; ^{emilie.duvallet@univ-paris13.fr} ; Eric  ; Assier^b ;   ; ^{eric.assier@univ-paris13.fr} ; Luca  ; Semerano^b ;   ; ^c ;   ; ^{luca.semerano@avc.aphp.fr} ; Laure  ; Delavallé ; e^b ;   ; ^{laure.delavallee@upmc.fr} ; Natacha  ; Bessis^b ;   ; ^{natacha.bessis@univ-paris13.fr} ; Jean-Franç ; ois  ; Zagury^a ;   ; ¹ ;   ; ^{zagury@cnam.fr} ; Marie-Christophe  ; Boissier^b ;   ; ^c ;   ; ¹ ;   ; ^{boissier@univ-paris13.fr}
• 关键词：IL-23p19 ; Peptides ; Vaccination ; Rheumatoid arthritis
• 刊名：Vaccine
• 出版年：2011
• 出版时间：21 November 2011
• 年：2011
• 卷：29
• 期：50
• 页码：9329-9336
• 全文大小：1026 K

文摘

Introduction

IL-23 is a pro-inflammatory cytokine essential for the differentiation of Th17 lymphocytes, a subtype of T lymphocyte implied in auto-immunity. IL-23 shares a subunit with IL-12, IL-12/23p40, and comprises a specific subunit, IL-23p19. We previously demonstrated that active immunization against entire TNF-¦Á and against peptides of IL-1¦Â was protective in animal models of rheumatoid arthritis. The aim of this study was to evaluate the effect of peptide-based vaccines targeting the IL-23p19 subunit in collagen-induced arthritis (CIA).

Methods

Using bioinformatics, the murine IL-23p19 subunit was modeled and two peptides were defined in the receptor interacting domain. Each peptide was coupled to keyhole limpet hemocyanin (KLH) to obtain two vaccines IL23-K1 and IL23-K2. Both vaccines were used for immunizations in incomplete Freund adjuvant (IFA) in groups of DBA/1 mice. Control groups received KLH or PBS at the same dates. CIA was induced by two subcutaneous injections of bovine type II collagen (CIIb), and the development of disease assessed during the next two months. Anti-CIIb and anti-IL-23 antibody levels were assessed by ELISA. Pro- and anti-inflammatory cytokines mRNA were quantified by qRT-PCR in the spleen and the synovium. T-cell populations in the spleen were evaluated by FACS analysis.

Results

The clinical scores showed that mice treated with IL23-K1 developed less arthritis than negative controls (p < 0.05). Mice immunized with IL23-K1 produced more anti-IL-23 antibodies than those immunized with IL23-K2 (p < 0.001). mRNA quantification showed that the IL23-K1 immunization led to an increase of IL-10 in the spleen (p < 0.05 vs KLH), without any effect on IL-17 level. Histological examination showed that IL23-K1 strongly protected against joint destruction and inflammation (p < 0.01 vs KLH and p < 0.001 vs PBS). T-cell populations in the spleen were not modified by IL-23 modulation.

Conclusion

These data show that targeting IL-23p19 through a vaccination strategy is protective in CIA. This specific targeting of IL-23 might constitute a promising therapeutic approach to explore in rheumatoid arthritis.