Epinephrine Production in Th17 Cells and Experimental Autoimmune Encephalitis.
Fiche publication
Date publication
janvier 2021
Journal
Frontiers in immunology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre
Tous les auteurs :
Yang P, Tian H, Zou YR, Chambon P, Ichinose H, Honig G, Diamond B, Kim SJ
Lien Pubmed
Résumé
Epinephrine is a hormone secreted primarily by medullary cells of the adrenal glands which regulates permeability of blood-brain barrier (BBB). Recent studies showed signaling by epinephrine/epinephrine receptor in T cells is involved in autoimmune diseases. Nevertheless, the production of epinephrine by T cells and its pathogenic function in T cells are not well investigated. Our results show that phenylethanol N-methyltransferase (PNMT), a rate-limiting enzyme of epinephrine synthesis, is specifically expressed in differentiated T17 cells and in tissue-resident T17 cells. Indeed, expression levels of enzymes involved in epinephrine production are higher in T17 cells from animals after EAE induction. The induction of PNMT was not observed in other effector T cell subsets or regulatory T cells. Epinephrine producing T17 cells exhibit co-expression of GM-CSF, suggesting they are pathogenic T17 cells. To delineate the function of epinephrine-production in T17 cells, we generated a T17-specific knockout of tyrosine hydroxylase (Th) by breeding a Th-flox and a ROR-gt-CRE mouse (Th-CKO). Th-CKO mice are developmentally normal with an equivalent T lymphocyte number in peripheral lymphoid organs. Th-CKO mice also show an equivalent number of T17 cells and following differentiation. To test whether epinephrine-producing T17 cells are key for breaching the BBB, migration of T cells through mouse brain endothelial cells was investigated . Both epi+ wild-type and epi- T17 cells migrate through an endothelial cell barrier. Mice were immunized with MOG peptide to induce experimental autoimmune encephalitis (EAE) and disease progression was monitored. Although there is a reduced infiltration of CD4+ T cells in Th-CKO mice, no difference in clinical score was observed between Th-CKO and wild-type control mice. Increased neutrophils were observed in the central nervous system of Th-CKO mice, suggesting an alternative pathway to EAE progression in the absence of T17 derived epinephrine.
Mots clés
Th17, blood–brain barrier, epinephrine, experimental autoimmune encephalitis , tyrosine hydroxylase
Référence
Front Immunol. 2021 ;12:616583