Abstract
Interleukin 1β (IL-1β) is critical for the in vivo survival, expansion and effector function of IL-17-producing helper T (T(H)17) cells during autoimmune responses, including experimental autoimmune encephalomyelitis (EAE). However, the spatiotemporal role and cellular source of IL-1β during EAE pathogenesis are poorly defined. In the present study, we uncovered a T cell-intrinsic inflammasome that drives IL-1β production during T(H)17-mediated EAE pathogenesis. Activation of T cell antigen receptors induced expression of pro-IL-1β, whereas ATP stimulation triggered T cell production of IL-1β via ASC-NLRP3-dependent caspase-8 activation. IL-1R was detected on T(H)17 cells but not on type 1 helper T (T(H)1) cells, and ATP-treated T(H)17 cells showed enhanced survival compared with ATP-treated T(H)1 cells, suggesting autocrine action of T(H)17-derived IL-1β. Together these data reveal a critical role for IL-1β produced by a T(H)17 cell-intrinsic ASC-NLRP3-caspase-8 inflammasome during inflammation of the central nervous system.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adenosine Triphosphate / pharmacology
-
Animals
-
Apoptosis Regulatory Proteins / genetics
-
Apoptosis Regulatory Proteins / immunology*
-
Apoptosis Regulatory Proteins / metabolism
-
CARD Signaling Adaptor Proteins
-
CD4-Positive T-Lymphocytes / immunology
-
CD4-Positive T-Lymphocytes / metabolism
-
Carrier Proteins / genetics
-
Carrier Proteins / immunology
-
Carrier Proteins / metabolism
-
Caspase 8 / genetics
-
Caspase 8 / immunology
-
Caspase 8 / metabolism
-
Cell Survival / genetics
-
Cell Survival / immunology
-
Cells, Cultured
-
Encephalomyelitis, Autoimmune, Experimental / genetics
-
Encephalomyelitis, Autoimmune, Experimental / immunology*
-
Encephalomyelitis, Autoimmune, Experimental / metabolism
-
Flow Cytometry
-
Gene Expression / immunology
-
Immunoblotting
-
Inflammasomes / genetics
-
Inflammasomes / immunology
-
Inflammasomes / metabolism
-
Interleukin-17 / genetics
-
Interleukin-17 / immunology
-
Interleukin-17 / metabolism
-
Interleukin-1beta / genetics
-
Interleukin-1beta / immunology
-
Interleukin-1beta / metabolism
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Mice, Transgenic
-
NLR Family, Pyrin Domain-Containing 3 Protein
-
Reverse Transcriptase Polymerase Chain Reaction
-
Signal Transduction / genetics
-
Signal Transduction / immunology
-
T-Lymphocytes / drug effects
-
T-Lymphocytes / immunology*
-
T-Lymphocytes / metabolism
-
Th17 Cells / drug effects
-
Th17 Cells / immunology*
-
Th17 Cells / metabolism
Substances
-
Apoptosis Regulatory Proteins
-
CARD Signaling Adaptor Proteins
-
Carrier Proteins
-
Inflammasomes
-
Interleukin-17
-
Interleukin-1beta
-
NLR Family, Pyrin Domain-Containing 3 Protein
-
Nlrp3 protein, mouse
-
Pycard protein, mouse
-
Adenosine Triphosphate
-
Caspase 8