Cutting edge: critical role for PYCARD/ASC in the development of experimental autoimmune encephalomyelitis.
Multiple sclerosis is an autoimmune disease in which self-reactive T cells attack oligodendrocytes that myelinate axons in the CNS. Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, is dependent on caspase-1; however, the role of Nod-like receptors upstream of caspase-1 is unknown. Danger- and pathogen-associated molecular patterns activate Nod-like receptor 3, which activates caspase-1 through the adaptor protein, apoptosis-associated speck-like protein containing CARD (ASC). We report that the progression of EAE is dependent on ASC and caspase-1 but not Nod-like receptor 3. ASC(-/-) mice were even more protected from the progression of EAE than were caspase-1(-/-) mice, suggesting that an inflammasome-independent function of ASC contributes to the progression of EAE. We found that CD4(+) T cells deficient in ASC exhibited impaired survival; accordingly, ASC(-/-) mice had fewer myelin oligodendrocyte glycoprotein-specific T cells in the draining lymph nodes and CNS.
Shaw
Patrick J
PJ
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38104, USA.
Lukens
John R
JR
Burns
Samir
S
Chi
Hongbo
H
McGargill
Maureen A
MA
Kanneganti
Thirumala-Devi
TD
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D053468:CARD Signaling Adaptor Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000502:physiology; D020170:Caspase 1 / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000633:toxicity; D063308:Myelin-Oligodendrocyte Glycoprotein; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein
D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D016207:Cytokines; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D020170:Caspase 1