An anti-inflammatory nod-like receptor is required for microglia development

Celia E. Shiau, Kelly Monk, William Joo, William S. Talbot

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Microglia are phagocytic cells that form the basis of the brain@s immune system. They derive from primitive macrophages that migrate into the brain during embryogenesis, but the genetic control of microglial development remains elusive. Starting with a genetic screen in zebrafish, we show that the noncanonical NOD-like receptor (NLR) nlrc3-like is essential for microglial formation. Although most NLRs trigger inflammatory signaling, nlrc3-like acts cell autonomously in microglia precursor cells to suppress unwarranted inflammation in the absence of overt immune challenge. In nlrc3-like mutants, primitive macrophages initiate a systemic inflammatory response with increased proinflammatory cytokines and actively aggregate instead of migrating into thebrain to form microglia. NLRC3-like requires both its pyrin and NACHT domains, and it can bind the inflammasome component apoptosis-associated speck-like protein. Our studies suggest that NLRC3-like may regulate the inflammasome and other inflammatory pathways. Together, these results demonstrate that NLRC3-like prevents inappropriate macrophage activation, thereby allowing normal microglial development.

Original languageEnglish (US)
Pages (from-to)1342-1352
Number of pages11
JournalCell Reports
Volume5
Issue number5
DOIs
StatePublished - Dec 12 2013
Externally publishedYes

Fingerprint

Macrophages
Microglia
Inflammasomes
Anti-Inflammatory Agents
Brain
Macrophage Activation
Immune system
Zebrafish
Phagocytes
Embryonic Development
Immune System
Chemical activation
Apoptosis
Cytokines
Inflammation
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

An anti-inflammatory nod-like receptor is required for microglia development. / Shiau, Celia E.; Monk, Kelly; Joo, William; Talbot, William S.

In: Cell Reports, Vol. 5, No. 5, 12.12.2013, p. 1342-1352.

Research output: Contribution to journalArticle

Shiau, Celia E. ; Monk, Kelly ; Joo, William ; Talbot, William S. / An anti-inflammatory nod-like receptor is required for microglia development. In: Cell Reports. 2013 ; Vol. 5, No. 5. pp. 1342-1352.
@article{5ed6b2010cb3462d859abb119f992566,
title = "An anti-inflammatory nod-like receptor is required for microglia development",
abstract = "Microglia are phagocytic cells that form the basis of the brain@s immune system. They derive from primitive macrophages that migrate into the brain during embryogenesis, but the genetic control of microglial development remains elusive. Starting with a genetic screen in zebrafish, we show that the noncanonical NOD-like receptor (NLR) nlrc3-like is essential for microglial formation. Although most NLRs trigger inflammatory signaling, nlrc3-like acts cell autonomously in microglia precursor cells to suppress unwarranted inflammation in the absence of overt immune challenge. In nlrc3-like mutants, primitive macrophages initiate a systemic inflammatory response with increased proinflammatory cytokines and actively aggregate instead of migrating into thebrain to form microglia. NLRC3-like requires both its pyrin and NACHT domains, and it can bind the inflammasome component apoptosis-associated speck-like protein. Our studies suggest that NLRC3-like may regulate the inflammasome and other inflammatory pathways. Together, these results demonstrate that NLRC3-like prevents inappropriate macrophage activation, thereby allowing normal microglial development.",
author = "Shiau, {Celia E.} and Kelly Monk and William Joo and Talbot, {William S.}",
year = "2013",
month = "12",
day = "12",
doi = "10.1016/j.celrep.2013.11.004",
language = "English (US)",
volume = "5",
pages = "1342--1352",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - An anti-inflammatory nod-like receptor is required for microglia development

AU - Shiau, Celia E.

AU - Monk, Kelly

AU - Joo, William

AU - Talbot, William S.

PY - 2013/12/12

Y1 - 2013/12/12

N2 - Microglia are phagocytic cells that form the basis of the brain@s immune system. They derive from primitive macrophages that migrate into the brain during embryogenesis, but the genetic control of microglial development remains elusive. Starting with a genetic screen in zebrafish, we show that the noncanonical NOD-like receptor (NLR) nlrc3-like is essential for microglial formation. Although most NLRs trigger inflammatory signaling, nlrc3-like acts cell autonomously in microglia precursor cells to suppress unwarranted inflammation in the absence of overt immune challenge. In nlrc3-like mutants, primitive macrophages initiate a systemic inflammatory response with increased proinflammatory cytokines and actively aggregate instead of migrating into thebrain to form microglia. NLRC3-like requires both its pyrin and NACHT domains, and it can bind the inflammasome component apoptosis-associated speck-like protein. Our studies suggest that NLRC3-like may regulate the inflammasome and other inflammatory pathways. Together, these results demonstrate that NLRC3-like prevents inappropriate macrophage activation, thereby allowing normal microglial development.

AB - Microglia are phagocytic cells that form the basis of the brain@s immune system. They derive from primitive macrophages that migrate into the brain during embryogenesis, but the genetic control of microglial development remains elusive. Starting with a genetic screen in zebrafish, we show that the noncanonical NOD-like receptor (NLR) nlrc3-like is essential for microglial formation. Although most NLRs trigger inflammatory signaling, nlrc3-like acts cell autonomously in microglia precursor cells to suppress unwarranted inflammation in the absence of overt immune challenge. In nlrc3-like mutants, primitive macrophages initiate a systemic inflammatory response with increased proinflammatory cytokines and actively aggregate instead of migrating into thebrain to form microglia. NLRC3-like requires both its pyrin and NACHT domains, and it can bind the inflammasome component apoptosis-associated speck-like protein. Our studies suggest that NLRC3-like may regulate the inflammasome and other inflammatory pathways. Together, these results demonstrate that NLRC3-like prevents inappropriate macrophage activation, thereby allowing normal microglial development.

UR - http://www.scopus.com/inward/record.url?scp=84890162977&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890162977&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2013.11.004

DO - 10.1016/j.celrep.2013.11.004

M3 - Article

C2 - 24316075

AN - SCOPUS:84890162977

VL - 5

SP - 1342

EP - 1352

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 5

ER -