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In this study, we identify over 100 long noncoding RNAs that are differentially expressed within 24 h of Th1 cell activation. Among those, we show that suppression of Malat1 is a hallmark of CD4+ T cell activation, but its complete deletion results in more potent immune responses to infection. This is because Malat1\u2212\/\u2212 Th1 and Th2 cells express lower levels of the immunosuppressive cytokine IL-10. In vivo, the reduced CD4+ T cell IL-10 expression in Malat1\u2212\/\u2212mice underpins enhanced immunity and pathogen clearance in experimental visceral leishmaniasis (Leishmania donovani) but more severe disease in a model of malaria (Plasmodium chabaudi chabaudi AS). Mechanistically, Malat1 regulates IL-10 through enhancing expression of Maf, a key transcriptional regulator of IL-10. Maf expression correlates with Malat1 in single Ag-specific Th cells from P. chabaudi chabaudi AS\u2013infected mice and is downregulated in Malat1\u2212\/\u2212 Th1 and Th2 cells. The Malat1 RNA is responsible for these effects, as antisense oligonucleotide-mediated inhibition of Malat1 also suppresses Maf and IL-10 levels. Our results reveal that through promoting expression of the Maf\/IL-10 axis in effector Th cells, Malat1 is a nonredundant regulator of mammalian immunity.<\/jats:p>","DOI":"10.4049\/jimmunol.1900940","type":"journal-article","created":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T19:36:07Z","timestamp":1587584167000},"page":"2949-2960","source":"Crossref","is-referenced-by-count":70,"title":["<i>Malat1<\/i> Suppresses Immunity to Infection through Promoting Expression of Maf and IL-10 in Th Cells"],"prefix":"10.1093","volume":"204","author":[{"given":"James P","family":"Hewitson","sequence":"first","affiliation":[{"name":"York Biomedical Research Institute, University of York , York, YO10 5DD Yorkshire ,","place":["United Kingdom"]},{"name":"Department of Biology, University of York , York, YO10 5DD Yorkshire ,","place":["United 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