Mef2d potentiates type-2 immune responses and allergic lung inflammation.
Science
; 384(6703): eadl0370, 2024 Jun 28.
Article
in En
| MEDLINE
| ID: mdl-38935708
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pneumonia
/
Th2 Cells
/
GATA3 Transcription Factor
/
NFATC Transcription Factors
/
MEF2 Transcription Factors
/
Interleukin-33
/
Immunity, Innate
Limits:
Animals
Language:
En
Journal:
Science
Year:
2024
Document type:
Article
Affiliation country: