The transcription factor T-bet is induced by IL-15 and thymic agonist selection and controls CD8??(+) intraepithelial lymphocyte development.
21.08.2014
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;41(2):230-43.
CD8??+ intraepithelial lymphocytes (IELs) are instrumental in maintaining the epithelial barrier in the intestine.Similar to natural killer cells and other innate lymphoid cells, CD8??+ 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 TCR??+ and TCR??+ CD8??+ 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 CD8??+ IELs.
