{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T22:24:53Z","timestamp":1785795893188,"version":"3.56.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Epinephrine is a hormone secreted primarily by medullary cells of the adrenal glands which regulates permeability of blood\u2013brain 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 <jats:italic>in vitro<\/jats:italic> in differentiated T<jats:sub>H<\/jats:sub>17 cells and in tissue-resident T<jats:sub>H<\/jats:sub>17 cells. Indeed, expression levels of enzymes involved in epinephrine production are higher in T<jats:sub>H<\/jats:sub>17 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 T<jats:sub>H<\/jats:sub>17 cells exhibit co-expression of GM-CSF, suggesting they are pathogenic T<jats:sub>H<\/jats:sub>17 cells. To delineate the function of epinephrine-production in T<jats:sub>H<\/jats:sub>17 cells, we generated a T<jats:sub>H<\/jats:sub>17-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 T<jats:sub>H<\/jats:sub>17 cells <jats:italic>in vivo<\/jats:italic> and following <jats:italic>in vitro<\/jats:italic> differentiation. To test whether epinephrine-producing T<jats:sub>H<\/jats:sub>17 cells are key for breaching the BBB, migration of T cells through mouse brain endothelial cells was investigated <jats:italic>in vitro<\/jats:italic>. Both epi+ wild-type and epi- T<jats:sub>H<\/jats:sub>17 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 T<jats:sub>H<\/jats:sub>17 derived epinephrine.<\/jats:p>","DOI":"10.3389\/fimmu.2021.616583","type":"journal-article","created":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T04:38:02Z","timestamp":1613968682000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Epinephrine Production in Th17 Cells and Experimental Autoimmune 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