Mef2d potentiates type-2 immune responses and allergic lung inflammation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38935708.
- Also identified by DOI 10.1126/science.adl0370 and PMC identifier 7616247.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Innate lymphoid cells (ILCs) and adaptive T lymphocytes promote tissue homeostasis and protective immune responses. Their production depends on the transcription factor GATA3, which is further elevated specifically in ILC2s and T helper 2 cells to drive type-2 immunity during tissue repair, allergic disorders, and anti-helminth immunity. The control of this crucial up-regulation is poorly understood. Using CRISPR screens in ILCs we identified previously unappreciated myocyte-specific enhancer factor 2d (Mef2d)-mediated regulation of GATA3-dependent type-2 lymphocyte differentiation. Mef2d-deletion from ILC2s and/or T cells specifically protected against an allergen lung challenge. Mef2d repressed Regnase-1 endonuclease expression to enhance IL-33 receptor production and IL-33 signaling and acted downstream of calcium-mediated signaling to translocate NFAT1 to the nucleus to promote type-2 cytokine-mediated immunity.
Medical subject headings
- MEF2 Transcription Factors
- Th2 Cells
- Immunity, Innate
- Interleukin-33
- NFATC Transcription Factors
- Pneumonia
- GATA3 Transcription Factor