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Immunity. 2014 Aug 21;41(2):230-43. doi: 10.1016/j.immuni.2014.06.018.

The transcription factor T-bet is induced by IL-15 and thymic agonist selection and controls CD8αα(+) intraepithelial lymphocyte development.

Author information

1
Institute of Medical Microbiology and Hygiene, University of Freiburg Medical Center, 79104 Freiburg, Germany; Department of Internal Medicine IV, University of Freiburg Medical Center, 79106 Freiburg, Germany.
2
Institute of Medical Microbiology and Hygiene, University of Freiburg Medical Center, 79104 Freiburg, Germany; Institute of Medical Microbiology and Hygiene, University of Mainz Medical Center, 55131 Mainz, Germany.
3
Institute of Medical Microbiology and Hygiene, University of Freiburg Medical Center, 79104 Freiburg, Germany; Institute of Medical Microbiology and Hygiene, University of Mainz Medical Center, 55131 Mainz, Germany; International Max Planck Research School for Molecular and Cellular Biology, 79108 Freiburg, Germany.
4
Institute of Medical Microbiology and Hygiene, University of Freiburg Medical Center, 79104 Freiburg, Germany; Department of Internal Medicine IV, University of Freiburg Medical Center, 79106 Freiburg, Germany; Faculty of Biology, 79104 Freiburg, Germany.
5
Department of Internal Medicine IV, University of Freiburg Medical Center, 79106 Freiburg, Germany; BIOSS Center of Biological Signalling Studies, 79104 Freiburg, Germany.
6
Institute of Medical Microbiology and Hygiene, University of Mainz Medical Center, 55131 Mainz, Germany.
7
Laboratory of Transplantation Immunology, Departments of Biomedicine and Nephrology, University Hospital Basel, 4031 Basel, Switzerland.
8
Institute of Medical Microbiology and Hygiene, University of Freiburg Medical Center, 79104 Freiburg, Germany; Department of Internal Medicine IV, University of Freiburg Medical Center, 79106 Freiburg, Germany. Electronic address: yakup.tanriver@uniklinik-freiburg.de.

Abstract

CD8αα(+) intraepithelial lymphocytes (IELs) are instrumental in maintaining the epithelial barrier in the intestine. Similar to natural killer cells and other innate lymphoid cells, CD8αα(+) IELs constitutively express the T-box transcription factor T-bet. However, the precise role of T-bet for the differentiation or function of IELs is unknown. Here we show that mice genetically deficient for T-bet lacked both TCRαβ(+) and TCRγδ(+) CD8αα(+) IELs and thus are more susceptible to chemically induced colitis. Although T-bet was induced in thymic IEL precursors (IELPs) as a result of agonist selection and interleukin-15 (IL-15) receptor signaling, it was dispensable for the generation of IELPs. Subsequently, T-bet was required for the IL-15-dependent activation, differentiation, and expansion of IELPs in the periphery. Our study reveals a function of T-bet as a central transcriptional regulator linking agonist selection and IL-15 signaling with the emergence of CD8αα(+) IELs.

PMID:
25148024
DOI:
10.1016/j.immuni.2014.06.018
[Indexed for MEDLINE]
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