T-Cell-Intrinsic Receptor Interacting Protein 2 Regulates Pathogenic T Helper 17 Cell Differentiation.
Document Type
Article
Publication Date
11-20-2018
Keywords
JGM
JAX Source
Immunity 2018 Nov 20; 49(5):873-885.e7
Volume
49
Issue
5
First Page
873
Last Page
885
ISSN
1097-4180
PMID
30366765
DOI
https://doi.org/10.1016/j.immuni.2018.08.022
Abstract
Receptor interacting protein 2 (RIP2) plays a role in sensing intracellular pathogens, but its function in T cells is unclear. We show that RIP2 deficiency in CD4+ T cells resulted in chronic and severe interleukin-17A-mediated inflammation during Chlamydia pneumoniae lung infection, increased T helper 17 (Th17) cell formation in lungs of infected mice, accelerated atherosclerosis, and more severe experimental autoimmune encephalomyelitis. While RIP2 deficiency resulted in reduced conventional Th17 cell differentiation, it led to significantly enhanced differentiation of pathogenic (p)Th17 cells, which was dependent on RORα transcription factor and interleukin-1 but independent of nucleotide oligomerization domain (NOD) 1 and 2. Overexpression of RIP2 resulted in suppression of pTh17 cell differentiation, an effect mediated by its CARD domain, and phenocopied by a cell-permeable RIP2 CARD peptide. Our data suggest that RIP2 has a T cell-intrinsic role in determining the balance between homeostatic and pathogenic Th17 cell responses.
Recommended Citation
Shimada K,
Porritt R,
Markman J,
O'Rourke J,
Wakita D,
Noval Rivas M,
Ogawa C,
Kozhaya L,
Martins G,
Unutmaz D,
Baloh R,
Crother T,
Chen S,
Arditi M.
T-Cell-Intrinsic Receptor Interacting Protein 2 Regulates Pathogenic T Helper 17 Cell Differentiation. Immunity 2018 Nov 20; 49(5):873-885.e7