The Transcription Factor T Bet Is Induced by IL-15 and Thymic Agonist Selection and Controls CD8αα(+) Intraepithelial Lymphocyte Development

Klose CS, Blatz K, d’Hargues Y, Hernandez PP, Kofoed-Nielsen M, Ripka JF, Ebert K, Arnold SJ, Diefenbach A, Palmer E, Tanriver Y.

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

From Left to Right: Yakup Tanriver, Christoph S.N. Klose, and Katharina Blatz

From Left to Right: Yakup Tanriver, Christoph S.N. Klose, and Katharina Blatz

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.
PubMed: 25148024