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RESEARCH PRODUCT

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

Ed PalmerKarolina EbertYakup TanriverPedro P. HernandezPedro P. HernandezAndreas DiefenbachChristoph S.n. KloseSebastian J. ArnoldYannick D’harguesKatharina BlatzMichael Kofoed-nielsenMichael Kofoed-nielsenJuliane F. Ripka

subject

AgonistCD4-Positive T-Lymphocytesmedicine.drug_classCD8 AntigensReceptors Antigen T-Cell alpha-betaImmunologychemical and pharmacologic phenomenaBiologyCD8-Positive T-Lymphocytesdigestive systemMiceTRANSCRIPTION FACTOR TmedicineTranscriptional regulationImmunology and AllergyAnimalsIntestinal MucosaTranscription factorInterleukin-15Mice KnockoutReceptors Interleukin-15Innate lymphoid cellCell DifferentiationEpithelial CellsReceptors Antigen T-Cell gamma-deltahemic and immune systemsColitisCell biologyIntestinesMice Inbred C57BLInfectious DiseasesInterleukin 15ImmunologyIntraepithelial lymphocyteT-Box Domain ProteinstissuesFunction (biology)Signal Transduction

description

Summary 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.

yearjournalcountryeditionlanguage
2014-08-01Immunity
10.1016/j.immuni.2014.06.018http://dx.doi.org/10.1016/j.immuni.2014.06.018