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Res."],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Endotoxin tolerance (ET) is a protective mechanism in the process of sepsis, septic shock, and their sequelae including uncontrolled inflammation. Accumulating evidence has shown that peripheral T cells contribute to the induction of ET. However, what and how T-cell development contributes to ET inductions remain unclear.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Mice were intraperitoneally injected with LPS at a concentration of 5\u00a0mg\/kg to establish an LPS tolerance model and were divided into two groups: a group examined 72\u00a0h after LPS injection (72-h group) and a group examined 8\u00a0days after LPS injection (8-day group). Injection of PBS was used as a control. We performed high-throughput sequencing to analyze the characteristics and changes of CD4<jats:sup>+<\/jats:sup>SP\u00a0TCR<jats:italic>\u03b2<\/jats:italic>\u00a0CDR3 repertoires with respect to V direct to J rearrangement during the ET induction. Moreover, the proportion and proliferation, as well as surface molecules such as CD80 and CD86, of F4\/80<jats:sup>+<\/jats:sup> macrophages were analyzed using FCM. Furthermore, ACT assay was designed and administered by the tail vein into murine LPS-induced mouse model to evaluate the role of F4\/80<jats:sup>+<\/jats:sup> macrophages on the development of CD4<jats:sup>+<\/jats:sup>SP thymocytes in ET condition.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We found that the frequency and characteristics of the TCR<jats:italic>\u03b2<\/jats:italic> chain CDR3 changed obviously under condition of ET, indicating the occurrence of TCR rearrangement and thymocyte diversification. Moreover, the absolute numbers of F4\/80<jats:sup>+<\/jats:sup> macrophages, but not other APCs, were increased in thymic medulla at 72-h group, accompanied by the elevated function-related molecules of F4\/80<jats:sup>+<\/jats:sup> macrophages. Furthermore, adoptively transferred OVA<jats:sub>332-339<\/jats:sub> peptide-loaded macrophages into Rag-1<jats:sup>\u2212\/\u2212<\/jats:sup> mice induced the clone deletion of OVA-specific CD4<jats:sup>+<\/jats:sup>SP, thereby ameliorating the pathology in lung tissue in LPS challenge.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>These data reveal that the frequency and characteristics of the TCR<jats:italic>\u03b2<\/jats:italic> chain CDR3 undergo dynamic programming under conditions of LPS tolerance. Furthermore, the peripheral macrophages may be a key factor which carry peripheral antigen to thymic medulla and affect the negative selection of T-cell population, thereby contributing to the formation of ET. These results suggest that the clone selection in thymus in ET may confer protection against microbial sepsis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00011-022-01685-w","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T12:08:32Z","timestamp":1673525312000},"page":"531-540","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["TCR repertoire landscape reveals macrophage-mediated clone deletion in endotoxin tolerance"],"prefix":"10.1007","volume":"72","author":[{"given":"Juanjuan","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YiJing","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MengMeng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenke","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixu","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,1,12]]},"reference":[{"key":"1685_CR1","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/j.it.2009.07.009","volume":"30","author":"SK Biswas","year":"2009","unstructured":"Biswas SK, Lopez-Collazo E. 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