{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:01:50Z","timestamp":1791403310891,"version":"4.3.3"},"reference-count":43,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,5,5]]},"abstract":"<jats:p>Lrrc8a is a ubiquitously expressed gene that encodes a leucine-rich repeat (LRR)\u2013containing protein detected at higher levels on the surface of thymocytes than on other immune cells. We generated Lrrc8a\u2212\/\u2212 mice to investigate the role of LRRC8A in lymphocyte development and function. Lrrc8a\u2212\/\u2212 mice had increased prenatal and postnatal mortality, growth retardation, and multiple tissue abnormalities. Lrrc8a\u2212\/\u2212 mice displayed a modest block in B cell development but intact intrinsic B cell function. In contrast, both Lrrc8a\u2212\/\u2212 mice and Lrrc8a\u2212\/\u2212\u2192Rag2\u2212\/\u2212 bone marrow chimeras exhibited a severe cell-intrinsic block in early thymic development, with decreased proliferation and increased apoptosis of thymocytes, and impaired peripheral T cell function. Thymic epithelial cells expressed an LRRC8A ligand that was critical for double-negative to double-positive thymocyte differentiation and survival in vitro. LRRC8A constitutively associated with the GRB2\u2013GAB2 complex and lymphocyte-specific protein tyrosine kinase (LCK) in thymocytes. LRRC8A ligation activated AKT via the LCK\u2013ZAP\u201370\u2013GAB2\u2013PI3K pathway, and AKT phosphorylation was markedly reduced in the thymus of Lrrc8a\u2212\/\u2212 mice. These findings reveal an essential role for LRRC8A in T cell development, survival, and function.<\/jats:p>","DOI":"10.1084\/jem.20131379","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T03:30:24Z","timestamp":1398137424000},"page":"929-942","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":126,"title":["Leucine-rich repeat containing 8A (LRRC8A) is essential for T lymphocyte development and function"],"prefix":"10.1084","volume":"211","author":[{"given":"Lalit","family":"Kumar","sequence":"first","affiliation":[{"name":"Division of Immunology 1 and 2 ; and 3 , 4 , and 5"},{"name":"Joint Program in Transfusion Medicine, Division of Laboratory Medicine, Boston Children\u2019s Hospital 1 and 2 ; and 3 , 4 , and 5"},{"name":"Department of Pediatrics 1 and 2 ; and 3 , 4 , and 5"},{"name":"Department of Microbiology and Immunobiology 1 and 2 ; and 3 , 4 , and 5"},{"name":"Department of Pathology, Harvard Medical School, Boston, MA 02115 1 and 2 ; 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