4.7 Review

Role of Tet2 in Regulating Adaptive and Innate Immunity

Journal

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.665897

Keywords

ten-eleven translocation-2; DNA methylation; gene regulation and expression; immune cell differentiation; autoinflammatory and autoimmune diseases

Funding

  1. National Natural Science Foundation of China [82070813, 81873634, 81400783]
  2. National Key R&D Program of China [2016YFC1305000, 2016YFC1305001]
  3. Hunan Province Natural Science Foundation of China [2018JJ2573, 2020JJ2053]

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Epigenetic modifications, particularly DNA methylation regulated by TET enzymes, play crucial roles in regulating gene expression and have been implicated in the development of autoimmune and autoinflammatory diseases. The TET family proteins, especially Tet2, function as gene regulators and have potential as antitumor drug targets due to their ability to oxidize methylcytosine to hydroxymethylcytosine. Further research on Tet2 in immune response regulation and its effects on inflammatory gene expression may provide new therapeutic targets for related diseases.
Accumulated evidence indicates that epigenetic modifications play central roles in gene expression regulation and participate in developing many autoimmune and autoinflammatory diseases. Mechanistically, epigenetic modifications act as a bridge between environmental and cellular factors and susceptibility genes. DNA methylation is a critical epigenetic modification that is regulated by ten-eleven translocation (TET) enzymes. Accumulating evidence has revealed that TET family proteins function as gene regulators and antitumor drug targets mainly because of their ability to oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Recently, the effect of Tet2, an essential TET protein, on the development of autoimmune diseases has been explored. In this review, we summarize the current understanding of Tet2 in immune response regulation, clarify the mechanisms of Tet2 in B and T cell differentiation and function, and discuss the opposing effects of Tet2 on inflammatory gene expression in the immune system to provide new potential therapeutic targets for related diseases.

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