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

Publication ,  Journal Article
Inoue, M; Williams, KL; Gunn, MD; Shinohara, ML
Published in: Proc Natl Acad Sci U S A
June 26, 2012

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 up-regulate 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.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

June 26, 2012

Volume

109

Issue

26

Start / End Page

10480 / 10485

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Mice, Knockout
  • Mice
  • Encephalomyelitis, Autoimmune, Experimental
  • Chemotaxis
  • Central Nervous System
  • Cell Proliferation
  • Carrier Proteins
  • Animals
 

Citation

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Chicago
ICMJE
MLA
NLM
Inoue, M., Williams, K. L., Gunn, M. D., & Shinohara, M. L. (2012). NLRP3 inflammasome induces chemotactic immune cell migration to the CNS in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A, 109(26), 10480–10485. https://doi.org/10.1073/pnas.1201836109
Inoue, Makoto, Kristi L. Williams, Michael D. Gunn, and Mari L. Shinohara. “NLRP3 inflammasome induces chemotactic immune cell migration to the CNS in experimental autoimmune encephalomyelitis.Proc Natl Acad Sci U S A 109, no. 26 (June 26, 2012): 10480–85. https://doi.org/10.1073/pnas.1201836109.
Inoue M, Williams KL, Gunn MD, Shinohara ML. NLRP3 inflammasome induces chemotactic immune cell migration to the CNS in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10480–5.
Inoue, Makoto, et al. “NLRP3 inflammasome induces chemotactic immune cell migration to the CNS in experimental autoimmune encephalomyelitis.Proc Natl Acad Sci U S A, vol. 109, no. 26, June 2012, pp. 10480–85. Pubmed, doi:10.1073/pnas.1201836109.
Inoue M, Williams KL, Gunn MD, Shinohara ML. NLRP3 inflammasome induces chemotactic immune cell migration to the CNS in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10480–10485.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

June 26, 2012

Volume

109

Issue

26

Start / End Page

10480 / 10485

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Mice, Knockout
  • Mice
  • Encephalomyelitis, Autoimmune, Experimental
  • Chemotaxis
  • Central Nervous System
  • Cell Proliferation
  • Carrier Proteins
  • Animals