Malat1 Suppresses Immunity to Infection through Promoting Expression of Maf and IL-10 in Th Cells

J Immunol. 2020 Jun 1;204(11):2949-2960. doi: 10.4049/jimmunol.1900940. Epub 2020 Apr 22.


Despite extensive mapping of long noncoding RNAs in immune cells, their function in vivo remains poorly understood. 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-/- 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-/- mice 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-infected mice and is downregulated in Malat1-/- 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Gene Expression Regulation
  • Humans
  • Immune Tolerance
  • Immunity / genetics
  • Interleukin-10 / metabolism*
  • Leishmania donovani / physiology*
  • Leishmaniasis, Visceral / immunology*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Proto-Oncogene Proteins c-maf / genetics
  • Proto-Oncogene Proteins c-maf / metabolism*
  • RNA, Long Noncoding / genetics*
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*
  • Up-Regulation


  • Maf protein, mouse
  • Malat1 long non-coding RNA, mouse
  • Proto-Oncogene Proteins c-maf
  • RNA, Long Noncoding
  • Interleukin-10