Unlike αβ T cells, γδ T cells, LTi cells and NKT cells do not require IRF4 for the production of IL‐17A and IL‐22

Medientyp: E-Artikel
Titel: Unlike αβ T cells, γδ T cells, LTi cells and NKT cells do not require IRF4 for the production of IL‐17A and IL‐22
Beteiligte: Raifer, Hartmann; Mahiny, Azita J.; Bollig, Nadine; Petermann, Franziska; Hellhund, Anne; Kellner, Kerstin; Guralnik, Anna; Reinhard, Katharina; Bothur, Evita; Huber, Magdalena; Bauer, Stefan; Löhning, Max; Kiss, Elina A.; Ganal, Stephanie C.; Diefenbach, Andreas; Korn, Thomas; Lohoff, Michael
Erschienen: Wiley, 2012
Erschienen in: European Journal of Immunology
Sprache: Englisch
DOI: 10.1002/eji.201142155
ISSN: 1521-4141; 0014-2980
Schlagwörter: Immunology ; Immunology and Allergy
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Beschreibung: <jats:p>Apart from conventional <jats:styled-content style="fixed-case">CD</jats:styled-content>4<jats:sup>+</jats:sup> <jats:styled-content style="fixed-case">T</jats:styled-content>h17 cells, the cytokines <jats:styled-content style="fixed-case">IL</jats:styled-content>‐17<jats:styled-content style="fixed-case">A</jats:styled-content> and <jats:styled-content style="fixed-case">IL</jats:styled-content>‐22 can also be produced by γδ <jats:styled-content style="fixed-case">T</jats:styled-content> cells, <jats:styled-content style="fixed-case">NK</jats:styled-content> cells and lymphoid tissue inducer (LTi) cells. <jats:styled-content style="fixed-case">T</jats:styled-content>h17 cells develop from precursor cells after <jats:styled-content style="fixed-case">T</jats:styled-content>‐cell receptor stimulation in the presence of <jats:styled-content style="fixed-case">TGF</jats:styled-content>‐β, <jats:styled-content style="fixed-case">IL</jats:styled-content>‐6 and <jats:styled-content style="fixed-case">IL</jats:styled-content>‐23. In contrast, a subset of γδ <jats:styled-content style="fixed-case">T</jats:styled-content> cells (“γδ<jats:styled-content style="fixed-case">T</jats:styled-content>17”) is committed for fast <jats:styled-content style="fixed-case">IL</jats:styled-content>‐17 production already in the thymus; however, γδ <jats:styled-content style="fixed-case">T</jats:styled-content> cells can also produce <jats:styled-content style="fixed-case">IL</jats:styled-content>‐17 after prolonged in vitro stimulation via their γδ <jats:styled-content style="fixed-case">T</jats:styled-content>‐cell receptor plus <jats:styled-content style="fixed-case">IL</jats:styled-content>‐23. Here, we show that γδ <jats:styled-content style="fixed-case">T</jats:styled-content>‐, LTi‐ and <jats:styled-content style="fixed-case">NKT</jats:styled-content> cells differ extensively from <jats:styled-content style="fixed-case">T</jats:styled-content>h17 cells in their signalling requirements for the generation of <jats:styled-content style="fixed-case">IL</jats:styled-content>‐17<jats:styled-content style="fixed-case">A</jats:styled-content> and <jats:styled-content style="fixed-case">IL</jats:styled-content>‐22. While production of these cytokines by <jats:styled-content style="fixed-case">T</jats:styled-content>h17 cells totally depends on the transcription factor interferon regulatory factor 4 (<jats:styled-content style="fixed-case">IRF</jats:styled-content>4), <jats:styled-content style="fixed-case">IRF</jats:styled-content>4 is irrelevant in the other cell types. As for γδ <jats:styled-content style="fixed-case">T</jats:styled-content> cells, this finding pertains to both thymic commitment and prolonged in vitro culture. Furthermore, <jats:styled-content style="fixed-case">IL</jats:styled-content>‐17<jats:styled-content style="fixed-case">A</jats:styled-content>‐producing γδ <jats:styled-content style="fixed-case">T</jats:styled-content> cells accumulate in the central nervous system of <jats:styled-content style="fixed-case">IRF</jats:styled-content>4 deficient (<jats:italic>Irf4</jats:italic><jats:sup>−/−</jats:sup>) mice during experimental autoimmune encephalomyelitis. <jats:styled-content style="fixed-case">IL</jats:styled-content>‐17<jats:styled-content style="fixed-case">A</jats:styled-content>‐producing WT and <jats:italic>Irf4</jats:italic><jats:sup>−/−</jats:sup> γδ <jats:styled-content style="fixed-case">T</jats:styled-content> cells equally express <jats:styled-content style="fixed-case">CCR</jats:styled-content>6 and lack <jats:styled-content style="fixed-case">CD</jats:styled-content>27. The underlying <jats:styled-content style="fixed-case">IRF</jats:styled-content>4‐independent pathway partially involves <jats:styled-content style="fixed-case">STAT</jats:styled-content>3 during in vitro stimulation.</jats:p>
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