Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: HLA-B27/hβ2m transgenic rats (B27 rats), a model of spondylarthritis (SpA) develop spontaneous colitis and arthritis. Recently, in vitro studies demonstrated that altered dendritic cells (DCs) function promoted a biased expansion of pro-inflammatory Th17 cells and alterations of regulatory CD4+ T cells (Treg) function, characterized by heightened IL-17 and decreased Il-10 production. Interestingly, in vitro blockade of ICOS-ICOSL interaction reversed IL-10/IL-17 imbalanced production by Treg. These data led us to investigate the in vivo consequences of ICOS/ICOSL interaction in experimental SpA using a genetic approach by producing B27 rats with Icos deletion (B27.ICOS-/- rats).
Methods: ICOS-/- rats were produced using TALEN technology, and backcrossed onto the B27 transgenic background (F344). B27.ICOS+/+ and B27.ICOS-/- rats were weekly weighted, examined and scored for clinical symptoms (colitis, arthritis, alopecia and orchitis). Inflammatory pattern was determined by histological analysis and ex-vivo production of pro-inflammatory cytokines.
Results: As expected, chronic diarrhea was the most common manifestation, starting at 9 weeks of age in all B27.ICOS+/+ rats. Arthritis and alopecia developed only in some B27.ICOS+/+ rats. The clinical score progressively worsened in B27.ICOS+/+ rats. In contrast, the B27-ICOS-/- rats did not develop any symptom of disease until age of 16 weeks and attenuated symptoms were observed until 24 weeks, a finding that was confirmed by histopathology analysis. Decreased in vitro production of pro-inflammatory cytokines and increased IL-10 production by CD4+ T cells were consistently observed in the B27-ICOS-/- rats.
Conclusion: Those results indicate a protective effect of Icos deletion on the onset and severity of SpA in the B27 rat. The protective effect was associated to a decrease of pro-inflammatory T cells and an increased proportion of IL-10-producing CD4+T cells. Those data corroborate previous observation suggesting a key role for ICOS signaling in the imbalanced production of IL-10 and IL-17 by Treg in the B27 rat and highlight ICOS as a putative therapeutic target in SpA.
To cite this abstract in AMA style:Krause L, Jouhault Q, Cherqaoui B, Jobart-Malfait A, Anegon I, Chiocchia G, Breban MA. Modulator Role of Inducible Costimulator (ICOS) in Spondyloarthritis Animal Model [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/modulator-role-of-inducible-costimulator-icos-in-spondyloarthritis-animal-model/. Accessed October 27, 2020.
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