Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Endoplasmic Reticulum Aminopeptidase (ERAP) Deficiency Alters IL-17 Production and Host Response Following Yersinia Gastrointestinal Infection in B27-Transgenic Mice.
Inman1, Robert D., Zhu2, Fei
Recent genetic studies have demonstrated that polymorphisms in ERAP are strongly associated with spondyloarthritis. But the mechanism of this interaction has not been resolved. In the present study we examine the host immune response to Yersinia enterocolitica (Ye) using mice with genetic alteration of class I MHC or ERAP.
The following mice (all on a B6 background) were compared: (i) deficient in endogenous class I MHC (DKO) (ii) transgenic for HLA B*2705 (B27) (iii) transgenic for B*2705/human b2M (B27/b2M) (iii) transgenic for HLA B*2705 and deficient in ERAP (B27/ERAP-/-). Mice were challenged intragastrically with 107 Yersinia enterocolitica 0:8. Survival curves were generated and cytokine responses were assessed by quantitative PCR on mesenteric lymph nodes and liver.
Survival curve (figure1) indicated the following ranking: B27/b2M> B27/ERAP-/- > B27> DKO. Only DKO showed significant effects (<3 days) on early survival, confirming that ERAP effects on host immune responses implicate adaptive immunity not innate immunity. With respect to cytokine profiles, the clearest differential was an elevated expression of IL-17 in B27/ERAP-/- mice, which coincided with the temporal course of mortality. There was no consistent impact of ERAP deficiency on IL-4, IL-23, IFN-g, TGF-b, or TNF-a after Yersinia infection.
ERAP deficiency was associated with enhanced IL-17 production after gastrointestinal infection with Yersinia (figure2). These findings suggest that polymorphisms which affect ERAP function might play a deleterious role in IL-17-mediated immune responses to arthritogenic pathogens.
To cite this abstract, please use the following information:
Inman, Robert D., Zhu, Fei; Endoplasmic Reticulum Aminopeptidase (ERAP) Deficiency Alters IL-17 Production and Host Response Following Yersinia Gastrointestinal Infection in B27-Transgenic Mice. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1969