Recirculating Foxp3 + regulatory T cells are restimulated in the thymus under Aire control.

Autor: Charaix J; Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University, CNRS, INSERM, CIML, Marseille, France., Borelli A; Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University, CNRS, INSERM, CIML, Marseille, France., Santamaria JC; Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University, CNRS, INSERM, CIML, Marseille, France., Chasson L; Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University, CNRS, INSERM, CIML, Marseille, France., Giraud M; Center for Research in Transplantation and Translational Immunology, UMR 1064, INSERM, Nantes Université, 44000, Nantes, France., Sergé A; Turing Centre for Living Systems, Laboratoire adhésion inflammation (LAI), CNRS, INSERM, Aix-Marseille University, 13288, Marseille, France., Irla M; Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University, CNRS, INSERM, CIML, Marseille, France. Magali.Irla@inserm.fr.
Jazyk: angličtina
Zdroj: Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2022 Jun 09; Vol. 79 (7), pp. 355. Date of Electronic Publication: 2022 Jun 09.
DOI: 10.1007/s00018-022-04328-9
Abstrakt: Thymically-derived Foxp3 + regulatory T cells (T reg ) critically control immunological tolerance. These cells are generated in the medulla through high affinity interactions with medullary thymic epithelial cells (mTEC) expressing the Autoimmune regulator (Aire). Recent advances have revealed that thymic T reg contain not only developing but also recirculating cells from the periphery. Although Aire is implicated in the generation of Foxp3 + T reg , its role in the biology of recirculating T reg remains elusive. Here, we show that Aire regulates the suppressive signature of recirculating T reg independently of the remodeling of the medullary 3D organization throughout life where T reg reside. Accordingly, the adoptive transfer of peripheral Foxp3 + T reg in Aire KO recipients led to an impaired suppressive signature upon their entry into the thymus. Furthermore, recirculating T reg from Aire KO mice failed to attenuate the severity of multiorgan autoimmunity, demonstrating that their suppressive function is altered. Using bone marrow chimeras, we reveal that mTEC-specific expression of Aire controls the suppressive signature of recirculating T reg . Finally, mature mTEC lacking Aire were inefficient in stimulating peripheral T reg both in polyclonal and antigen-specific co-culture assays. Overall, this study demonstrates that Aire confers to mTEC the ability to restimulate recirculating T reg , unravelling a novel function for this master regulator in T reg biology.
(© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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