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Alliance"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:p>\n                    ICOS is a T-cell costimulatory receptor critical for Tfh cell generation and function. However, the role of ICOS in Tfr cell differentiation remains unclear. Using Foxp3-Cre\u2013mediated ICOS knockout (ICOS FC) mice, we show that ICOS deficiency in Treg-lineage cells drastically reduces the number of Tfr cells during GC reactions but has a minimal impact on conventional Treg cells. Single-cell transcriptome analysis of Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    cells at an early stage of the GC reaction suggests that ICOS normally inhibits\n                    <jats:italic>Klf2<\/jats:italic>\n                    expression to promote follicular features including\n                    <jats:italic>Bcl6<\/jats:italic>\n                    up-regulation. Furthermore, ICOS costimulation promotes nuclear localization of NFAT2, a known driver of CXCR5 expression. Notably, ICOS FC mice had an unaltered overall GC B-cell output but showed signs of expanded autoreactive B cells along with elevated autoantibody titers. Thus, our study demonstrates that ICOS costimulation is critical for Tfr cell differentiation and highlights the importance of Tfr cells in maintaining humoral immune tolerance during GC reactions.\n                  <\/jats:p>","DOI":"10.26508\/lsa.202201615","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T12:12:00Z","timestamp":1675858320000},"page":"e202201615","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":25,"title":["ICOS costimulation is indispensable for the differentiation of T follicular regulatory cells"],"prefix":"10.26508","volume":"6","author":[{"given":"Vincent","family":"Panneton","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05m8pzq90","id-type":"ROR","asserted-by":"publisher"}],"name":"Institut de Recherches Cliniques de Montr\u00e9al","place":[", Quebec, Canada"]},{"name":"Department of Microbiology, Infectiology and Immunology, University of 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