The Transcription Factor T-bet Is Induced by IL-15 and Thymic Agonist Selection and Controls CD8αα+ Intraepithelial Lymphocyte Development
| Autor: | Ed Palmer, Karolina Ebert, Yakup Tanriver, Pedro P. Hernandez, Andreas Diefenbach, Christoph S.N. Klose, Sebastian J. Arnold, Yannick d’Hargues, Katharina Blatz, Michael Kofoed-Nielsen, Juliane F. Ripka |
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| Jazyk: | angličtina |
| Předmět: |
Agonist
CD4-Positive T-Lymphocytes medicine.drug_class CD8 Antigens Receptors Antigen T-Cell alpha-beta Immunology chemical and pharmacologic phenomena Biology CD8-Positive T-Lymphocytes digestive system Mice TRANSCRIPTION FACTOR T medicine Transcriptional regulation Immunology and Allergy Animals Intestinal Mucosa Transcription factor Interleukin-15 Mice Knockout Receptors Interleukin-15 Innate lymphoid cell Cell Differentiation Epithelial Cells Receptors Antigen T-Cell gamma-delta hemic and immune systems Colitis Cell biology Intestines Mice Inbred C57BL Infectious Diseases Interleukin 15 Intraepithelial lymphocyte T-Box Domain Proteins tissues Function (biology) Signal Transduction |
| Zdroj: | Immunity. (2):230-243 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2014.06.018 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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