CX3CR1+ mononuclear phagocytes support colitis-associated innate lymphoid cell production of IL-22

Randy S. Longman, Gretchen E. Diehl, Daniel A. Victorio, Jun R. Huh, Carolina Galan, Emily R. Miraldi, Arun Swaminath, Richard Bonneau, Ellen J. Scherl, Dan R. Littman

Research output: Contribution to journalArticle

Abstract

Interleukin (IL)-22-producing group 3 innate lymphoid cells (ILC3) promote mucosal healing and maintain barrier integrity, but how microbial signals are integrated to regulate mucosal protection offered by these cells remains unclear. Here, we show that in vivo depletion of CX3CR1+ mononuclear phagocytes (MNPs) resulted in more severe colitis and death after infection with Citrobacter rodentium. This phenotype was rescued by exogenous IL-22, which was endogenously produced by ILC3 in close spatial proximity to CX3CR1+ MNPs that were dependent on MyD88 signaling. CX3CR1+ MNPs from both mouse and human tissue produced more IL-23 and IL-1β than conventional CD103+ dendritic cells (cDCs) and were more efficient than cDCs in supporting IL-22 production in ILC3 in vitro and in vivo. Further, colonic ILC3 from patients with mild to moderate ulcerative colitis or Crohn's disease had increased IL-22 production. IBD-associated SNP gene set analysis revealed enrichment for genes selectively expressed in human intestinal MNPs. The product of one of these, TL1A, potently enhanced IL-23- and IL-1β-induced production of IL-22 and GM-CSF by ILC3. Collectively, these results reveal a critical role for CX3CR1+ mononuclear phagocytes in integrating microbial signals to regulate colonic ILC3 function in IBD.

Original languageEnglish (US)
Pages (from-to)1571-1583
Number of pages13
JournalJournal of Experimental Medicine
Volume211
Issue number8
DOIs
StatePublished - 2014

Fingerprint

Colitis
Phagocytes
Lymphocytes
Interleukin-23
Interleukin-1
Dendritic Cells
Citrobacter rodentium
Cytoprotection
Granulocyte-Macrophage Colony-Stimulating Factor
Ulcerative Colitis
Crohn Disease
Genes
Single Nucleotide Polymorphism
interleukin-22
Phenotype
Infection

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Longman, R. S., Diehl, G. E., Victorio, D. A., Huh, J. R., Galan, C., Miraldi, E. R., ... Littman, D. R. (2014). CX3CR1+ mononuclear phagocytes support colitis-associated innate lymphoid cell production of IL-22. Journal of Experimental Medicine, 211(8), 1571-1583. https://doi.org/10.1084/jem.20140678

CX3CR1+ mononuclear phagocytes support colitis-associated innate lymphoid cell production of IL-22. / Longman, Randy S.; Diehl, Gretchen E.; Victorio, Daniel A.; Huh, Jun R.; Galan, Carolina; Miraldi, Emily R.; Swaminath, Arun; Bonneau, Richard; Scherl, Ellen J.; Littman, Dan R.

In: Journal of Experimental Medicine, Vol. 211, No. 8, 2014, p. 1571-1583.

Research output: Contribution to journalArticle

Longman, RS, Diehl, GE, Victorio, DA, Huh, JR, Galan, C, Miraldi, ER, Swaminath, A, Bonneau, R, Scherl, EJ & Littman, DR 2014, 'CX3CR1+ mononuclear phagocytes support colitis-associated innate lymphoid cell production of IL-22', Journal of Experimental Medicine, vol. 211, no. 8, pp. 1571-1583. https://doi.org/10.1084/jem.20140678
Longman, Randy S. ; Diehl, Gretchen E. ; Victorio, Daniel A. ; Huh, Jun R. ; Galan, Carolina ; Miraldi, Emily R. ; Swaminath, Arun ; Bonneau, Richard ; Scherl, Ellen J. ; Littman, Dan R. / CX3CR1+ mononuclear phagocytes support colitis-associated innate lymphoid cell production of IL-22. In: Journal of Experimental Medicine. 2014 ; Vol. 211, No. 8. pp. 1571-1583.
@article{30a30a84e744407ead3ec35ff1bf9821,
title = "CX3CR1+ mononuclear phagocytes support colitis-associated innate lymphoid cell production of IL-22",
abstract = "Interleukin (IL)-22-producing group 3 innate lymphoid cells (ILC3) promote mucosal healing and maintain barrier integrity, but how microbial signals are integrated to regulate mucosal protection offered by these cells remains unclear. Here, we show that in vivo depletion of CX3CR1+ mononuclear phagocytes (MNPs) resulted in more severe colitis and death after infection with Citrobacter rodentium. This phenotype was rescued by exogenous IL-22, which was endogenously produced by ILC3 in close spatial proximity to CX3CR1+ MNPs that were dependent on MyD88 signaling. CX3CR1+ MNPs from both mouse and human tissue produced more IL-23 and IL-1β than conventional CD103+ dendritic cells (cDCs) and were more efficient than cDCs in supporting IL-22 production in ILC3 in vitro and in vivo. Further, colonic ILC3 from patients with mild to moderate ulcerative colitis or Crohn's disease had increased IL-22 production. IBD-associated SNP gene set analysis revealed enrichment for genes selectively expressed in human intestinal MNPs. The product of one of these, TL1A, potently enhanced IL-23- and IL-1β-induced production of IL-22 and GM-CSF by ILC3. Collectively, these results reveal a critical role for CX3CR1+ mononuclear phagocytes in integrating microbial signals to regulate colonic ILC3 function in IBD.",
author = "Longman, {Randy S.} and Diehl, {Gretchen E.} and Victorio, {Daniel A.} and Huh, {Jun R.} and Carolina Galan and Miraldi, {Emily R.} and Arun Swaminath and Richard Bonneau and Scherl, {Ellen J.} and Littman, {Dan R.}",
year = "2014",
doi = "10.1084/jem.20140678",
language = "English (US)",
volume = "211",
pages = "1571--1583",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "8",

}

TY - JOUR

T1 - CX3CR1+ mononuclear phagocytes support colitis-associated innate lymphoid cell production of IL-22

AU - Longman, Randy S.

AU - Diehl, Gretchen E.

AU - Victorio, Daniel A.

AU - Huh, Jun R.

AU - Galan, Carolina

AU - Miraldi, Emily R.

AU - Swaminath, Arun

AU - Bonneau, Richard

AU - Scherl, Ellen J.

AU - Littman, Dan R.

PY - 2014

Y1 - 2014

N2 - Interleukin (IL)-22-producing group 3 innate lymphoid cells (ILC3) promote mucosal healing and maintain barrier integrity, but how microbial signals are integrated to regulate mucosal protection offered by these cells remains unclear. Here, we show that in vivo depletion of CX3CR1+ mononuclear phagocytes (MNPs) resulted in more severe colitis and death after infection with Citrobacter rodentium. This phenotype was rescued by exogenous IL-22, which was endogenously produced by ILC3 in close spatial proximity to CX3CR1+ MNPs that were dependent on MyD88 signaling. CX3CR1+ MNPs from both mouse and human tissue produced more IL-23 and IL-1β than conventional CD103+ dendritic cells (cDCs) and were more efficient than cDCs in supporting IL-22 production in ILC3 in vitro and in vivo. Further, colonic ILC3 from patients with mild to moderate ulcerative colitis or Crohn's disease had increased IL-22 production. IBD-associated SNP gene set analysis revealed enrichment for genes selectively expressed in human intestinal MNPs. The product of one of these, TL1A, potently enhanced IL-23- and IL-1β-induced production of IL-22 and GM-CSF by ILC3. Collectively, these results reveal a critical role for CX3CR1+ mononuclear phagocytes in integrating microbial signals to regulate colonic ILC3 function in IBD.

AB - Interleukin (IL)-22-producing group 3 innate lymphoid cells (ILC3) promote mucosal healing and maintain barrier integrity, but how microbial signals are integrated to regulate mucosal protection offered by these cells remains unclear. Here, we show that in vivo depletion of CX3CR1+ mononuclear phagocytes (MNPs) resulted in more severe colitis and death after infection with Citrobacter rodentium. This phenotype was rescued by exogenous IL-22, which was endogenously produced by ILC3 in close spatial proximity to CX3CR1+ MNPs that were dependent on MyD88 signaling. CX3CR1+ MNPs from both mouse and human tissue produced more IL-23 and IL-1β than conventional CD103+ dendritic cells (cDCs) and were more efficient than cDCs in supporting IL-22 production in ILC3 in vitro and in vivo. Further, colonic ILC3 from patients with mild to moderate ulcerative colitis or Crohn's disease had increased IL-22 production. IBD-associated SNP gene set analysis revealed enrichment for genes selectively expressed in human intestinal MNPs. The product of one of these, TL1A, potently enhanced IL-23- and IL-1β-induced production of IL-22 and GM-CSF by ILC3. Collectively, these results reveal a critical role for CX3CR1+ mononuclear phagocytes in integrating microbial signals to regulate colonic ILC3 function in IBD.

UR - http://www.scopus.com/inward/record.url?scp=84905118660&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84905118660&partnerID=8YFLogxK

U2 - 10.1084/jem.20140678

DO - 10.1084/jem.20140678

M3 - Article

C2 - 25024136

AN - SCOPUS:84905118660

VL - 211

SP - 1571

EP - 1583

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 8

ER -