Modulator Role of Inducible Costimulator (ICOS) in Spondyloarthritis Animal Model

Luiza Krause¹, Quentin Jouhault², Bilade Cherqaoui¹, Aude Jobart-Malfait¹, Ignacio Anegon³, Gilles Chiocchia⁴ and Maxime A. Breban⁵, ¹INSERM-U1173, University of Versailles Saint-Quentin-en-Yvelines, France, Montigny-le-Bretonneux, France, ²Infection and inflammation, INSERM-U1173, University of Versailles Saint-Quentin-en-Yvelines, France, Montigny-le-Bretonneux, France, ³U643, INSERM-UMR643- Nantes-CHU, Nantes, France, ⁴Infection and Inflammation, INSERM-U1173, University of Versailles Saint-Quentin-en-Yvelines, France, Montigny-le-Bretonneux, France, ⁵Rheumatology, Ambroise Paré Hospital, and Versailles Saint Quentin en Yvelines University, Boulogne-Billancourt, France

Meeting: ACR/ARHP Annual Meeting 2016

Date of first publication: September 28, 2016

Keywords: animal models and spondylarthritis, T cells

Session Information

Date: Tuesday, November 15, 2016

Title: Spondylarthropathies Psoriatic Arthritis – Pathogenesis, Etiology - Poster II

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.

Disclosure: L. Krause, None; Q. Jouhault, None; B. Cherqaoui, None; A. Jobart-Malfait, None; I. Anegon, None; G. Chiocchia, None; M. A. Breban, None.

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 .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/modulator-role-of-inducible-costimulator-icos-in-spondyloarthritis-animal-model/