Recruitment of CXCR3+ T cells into injured tissues in adult IgA vasculitis patients correlates with disease activity

Alexandra Audemard-Verger (1) , Evangeline Pillebout (2) , Agnès Jamin (2) , Laureline Berthelot (3) , Cédric Aufray (1) , Bruno Martin (1) , Aurélie Sannier (4) , Eric Daugas (2) , Julie Déchanet-Merville (5) , Yolande Richard (1) , Renato Monteiro (2) , Bruno Lucas (1)

1 IC UM3 (UMR 8104 / U1016) - Institut Cochin
2 CRI (UMR_S_1149 / ERL_8252 / U1149) - Centre de recherche sur l'Inflammation
3 Team 4 - U1064 Inserm - CRTI - Immunoregulation And Immunointervention in Transplantation and Autoimmunity
4 Département d'Anatomo-Pathologie [Hôpital Bichat]
5 ImmunoConcept - Immunology from Concept and Experiments to Translation

Objectives: Adult immunoglobulin A vasculitis (IgAV) is an immune complex small vessel vasculitis. So far, the involvement of T cells in this pathology has been poorly studied. The aim of this study was to analyze T-cell homeostasis as well as cytokine and chemokine concentrations in the blood and tissues of IgAV patients. Methods: T cells, cytokine and chemokine concentrations were analyzed in peripheral blood using flow cyto-metry and multiplex assays. T-cell infiltrates in the kidney and the skin were characterized by im-munohistochemistry. This study prospectively included 44 adult patients with biopsy-proven IgAV and 24 age-and sex-matched healthy controls. Results: We observed reduced proportions of circulating CXCR5-and CXCR3-expressing memory CD4 T cells at diagnosis but normal values at remission. The plasma levels of Th1-related cytokines (IL-12, IL-27 and IFNγ) and of the TFH-related cytokine, IL-21, were paradoxically not reduced in patients. We observed increased plasma concentrations of the CXCR5 ligand, CXCL13, and of the CXCR3 ligands, CXCL10/11, suggesting a potential relocation of the corresponding T cells into inflamed tissues. We then confirmed the recruitment of CXCR3-expressing T cells into the skin and kidneys. In the skin, T-cell infiltrates mainly co-localized with damaged dermal small vessels. Finally, patients with the largest kidney T-cell infiltrates were also those with the highest proteinuria. Conclusion: Altogether, our results strongly suggest that, in IgAV patients, CXCL10/11 orchestrate the recruitment of CXCR3-expressing T cells in injured tissues, contributing to tissue damage and disease activity.

Mots clés: Chemokines; Cytokines; T-cell infiltrates; IgA vasculitis; Helper T cells

Domaines: Médecine humaine et pathologie

Alexandra Audemard-Verger, Evangeline Pillebout, Agnès Jamin, Laureline Berthelot, Cédric Aufray, et al.. Recruitment of CXCR3+ T cells into injured tissues in adult IgA vasculitis patients correlates with disease activity. Journal of Autoimmunity, 2019, 99, pp.73-80. ⟨10.1016/j.jaut.2019.01.012⟩. ⟨inserm-02146095⟩