Liao, Chia-MinChia-MinLiaoZimmer, Michael I.Michael I.ZimmerShanmuganad, SharmilaSharmilaShanmuganadYu, Hon-TsenHon-TsenYuCardell, Susanna L.Susanna L.CardellWang, Chyung-RuChyung-RuWang2012-10-192018-07-062012-10-192018-07-06201200165085https://www.scopus.com/inward/record.uri?eid=2-s2.0-84856235126&doi=10.1053%2fj.gastro.2011.10.030&partnerID=40&md5=1aaec5412ec229b0408e97b2f0d99467http://ntur.lib.ntu.edu.tw//handle/246246/242917Background & Aims: CD1d-restricted natural killer (NK) T cells are a subset of immunoregulatory T cells that comprise type I (express the semi-invariant T-cell receptor [TCR] and can be detected using the α-galactosylceramide/CD1d tetramer) and type II (express diverse TCRs and cannot be directly identified). Studies in mouse models of inflammatory bowel disease revealed a complex role for type I NKT cells in the development of colitis. Type II NKT cells have been associated with intestinal inflammation in patients with ulcerative colitis. Methods: To investigate whether dysregulation of type II NKT cells, caused by increased expression of CD1d, can contribute to colitis, we generated transgenic mice that express high levels of CD1d and a TCR from an autoreactive, type II NKT cell (CD1dTg/24αβTg mice). Results: CD1dTg/24αβTg mice had reduced numbers of 24αβ T cells compared with 24αβTg mice, indicating that negative selection increases among type II NKT cells engaged by abundant self-antigen. The residual 24αβ T cells in CD1dTg/24αβTg mice had an altered surface phenotype and acquired a cytokine profile distinct from that of equivalent cells in 24αβTg mice. Interestingly, CD1dTg/24αβTg mice spontaneously developed colitis; adoptive transfer experiments confirmed that type II NKT cells that develop in the context of increased CD1d expression are pathogenic. Conclusions: Aberrant type II NKT cell responses directly contribute to intestinal inflammation in mice, indicating the importance of CD1d expression levels in the development and regulation of type II NKT cells. © 2012 AGA Institute.en-USCrohn's Disease; IBD; Immune Regulation; T-Cell DevelopmentCD1d antigen; gamma interferon; interleukin 13; interleukin 17; interleukin 4; T lymphocyte receptor; adoptive transfer; animal cell; animal experiment; animal model; animal tissue; article; cell selection; cell type; colitis; controlled study; cytokine production; disease course; lymphocyte function; mouse; natural killer T cell; nonhuman; phenotype; priority journal; protein expression; transgenic mousejournal article10.1053/j.gastro.2011.10.0302-s2.0-84856235126http://ntur.lib.ntu.edu.tw/bitstream/246246/242917/-1/21.pdf