Differential requirement for CARMA1 in agonist‐selected T‐cell development |
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| Authors: | Benjamin D Medoff Barry P Sandall Aimee Landry Kiyotaka Nagahama Atsushi Mizoguchi Andrew D Luster Ramnik J Xavier |
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| Institution: | 1. Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA;2. Pulmonary and Critical Care Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA;3. Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA;4. Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA, USA;5. Department of Experimental Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA;6. Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA |
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| Abstract: | Caspase recruitment domain‐containing membrane‐associated guanylate kinase protein‐1 (CARMA1) is a critical component of the NF‐κB signaling cascade mediated by TCR engagement. In addition to activation of naïve T cells, TCR signaling is important for the development of agonist‐selected T‐cell subsets such as Treg, NKT cells, and CD8‐αα T cells. However, little is known about the role of CARMA1 in the development of these lineages. Here we show that CARMA1‐deficient mice (CARMA1?/?) have altered populations of specific subsets of agonist‐selected T cells. Specifically, CARMA1?/? mice have impaired natural and adaptive Treg development, whereas NKT cell numbers are normal compared with wild‐type mice. Interestingly, CD8‐αα T cells, which may also be able to develop through an extrathymic selection pathway, are enriched in the gut of CARMA1?/? mice, whereas memory‐phenotype CD4+ T cells (CD62Llow/CD44high) are present at reduced numbers in the periphery. These results indicate that CARMA1 is essential for Treg development, but is not necessary for the development of other agonist‐selected T‐cell subsets. Overall, these data reveal an important but differential role for CARMA1‐mediated TCR signaling in T‐cell development. |
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| Keywords: | CARMA1 CD8‐α α T cell NKT cell Treg |
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