NLRP3 inflammasome induces chemotactic immune cell migration to the CNS in experimental autoimmune encephalomyelitis

Makoto Inoue, Kristi L. Williams, Michael D. Gunn, Mari L. Shinohara

Research output: Contribution to journalArticle

Abstract

The NLRP3 inflammasome is a multiprotein complex consisting of three kinds of proteins, NLRP3, ASC, and pro-caspase-1, and plays a role in sensing pathogens and danger signals in the innate immune system. The NLRP3 inflammasome is thought to be involved in the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). However, the mechanism by which the NLRP3 inflammasome induces EAE is not clear. In this study, we found that the NLRP3 inflammasome played a critical role in inducing T-helper cell migration into the CNS. To gain migratory ability, CD4+ T cells need to be primed by NLRP3 inflammasome-sufficient antigen-presenting cells to upregulate chemotaxis-related proteins, such as osteopontin, CCR2, and CXCR6. In the presence of the NLRP3 inflammasome, dendritic cells and macrophages also induce chemotactic ability and up-regulate chemotaxis-related proteins, such as α4β1 integrin, CCL7, CCL8, and CXCL16. On the other hand, reduced Th17 cell population size in immunized Nlrp3-/- and Asc-/- mice is not a determinative factor for their resistance to EAE. As currently applied in clinical interventions of MS, targeting immune cell migration molecules may be an effective approach in treating MS accompanied by NLRP3 inflammasome activation.

Original languageEnglish (US)
Pages (from-to)10480-10485
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number26
DOIs
StatePublished - Jun 26 2012
Externally publishedYes

Keywords

  • Demyelination
  • Intracerebroventricular injection
  • Intrathecal injection
  • Neuroinflammation
  • Passive experimental autoimmune encephalomyelitis

ASJC Scopus subject areas

  • General

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