General autoimmunity

Oral

Altered Treg Function and Selection Following Aire-deficiency, New Insights on the Role of Aire

Thursday, June 15
5:45 PM - 7:00 PM

Auto-immune diseases can be caused by a break in self-tolerance. The Auto-immune regulator (Aire) is an important transcription regulator that plays a critical role in central tolerance via promoting the expression of tissue restricted antigens in the thymus. The role of Aire on the selection and function of Tregs is still unresolved and controversial and its role in transplantation has never been addressed.


We demonstrated that there is a similar pattern of expression of Aire between rat and human in the thymus and lymph nodes. We then generated a model of Aire-deficient rats by disrupting 7-base pairs in exon 3 emulating a frequent human mutation. We observed that Aire-deficient rats displayed an APECED-like disease with strong auto-immune symptoms such as alopecia and vitiligo occurring at 6 month old, auto-immune histological injuries, numerous circulating auto-antibodies and a strong increase of circulating IgM and IgA. We demonstrated an altered suppressive capacity of both CD4+CD25+ and CD8+CD45RClow Tregs in Aire-/-rats in vitro in a MLR assay. Preliminary results from in-vivo model of wasting disease in IL2Rg-/- rats suggested that Tregs from Aire-/- rats failed to control the disease in contrast to Tregs from control rats. We also showed a significant bias in the TCR repertoire of CD8+CD45RClow Tregs with selection of a restricted private Vβ20 repertoire, but not in CD4+CD25hi Tregs. Altogether, our results demonstrate that Aire-deficient rats expressed APECED-type auto-immune features and suggest a role for Aire in Treg function and selection.

Jason Ossart

PhD student
Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France; LabEx IGO "Immunotherapy, Graft, Oncology"

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    Séverine Menoret

    Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France

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      Laure-Hélène Ouisse

      Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France

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        Elodie Autrusseau

        Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France

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          Claire Usal

          Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France

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            Anne Moreau

            Anatomie et Cytologie Pathologiques, CHU - Hôtel DIEU – NANTES, France

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              Marion Cadoux

              Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France

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                Cécile Braudeau

                CIMNA, Laboratoire d’Immunologie, CHU Nantes, Nantes, France

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                  Nicolas Degauque

                  Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France

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                    Jérôme Martin

                    Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France

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                      François-Xavier Hubert

                      Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France

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                        Ignacio Anegon

                        Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France

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                          Régis Josien

                          Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France

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                            Carole Guillonneau

                            CNRS
                            Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France

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