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PMID: 23453631 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Intraepithelial type 1 innate lymphoid cells are a unique subset of IL-12- and IL-15-responsive IFN-γ-producing cells.

Immunity ·Vol. 38 ·No. 4 ·2013-04-18 ·Pages 769-81

Fuchs A, Vermi W, Lee JS, Lonardi S, Gilfillan S, Newberry RD, Cella M, Colonna M

Abstract

Mucosal innate lymphoid cell (ILC) subsets promote immune responses to pathogens by producing distinct signature cytokines in response to changes in the cytokine microenvironment. We previously identified human ILC3 distinguished by interleukin-22 (IL-22) secretion. Here we characterized a human ILC1 subset that produced interferon-γ (IFN-γ) in response to IL-12 and IL-15 and had a unique integrin profile, intraepithelial location, hallmarks of TGF-β imprinting, and a memory-activated phenotype. Because tissue-resident memory CD8(+) T cells share this profile, intraepithelial ILC1 may be their innate counterparts. In mice, intraepithelial ILC1 were distinguished by CD160 expression and required Nfil3- and Tbx21-encoded transcription factors for development, but not IL-15 receptor-α, indicating that intraepithelial ILC1 are distinct from conventional NK cells. Intraepithelial ILC1 were amplified in Crohn's disease patients and contributed to pathology in the anti-CD40-induced colitis model in mice. Thus, intraepithelial ILC1 may initiate IFN-γ responses against pathogens but contribute to pathology when dysregulated.

MeSH Terms
Animals Antibodies, Monoclonal/administration & dosage CD40 Antigens/immunology Colitis/chemically induced,immunology Crohn Disease/immunology Disease Models, Animal Female Humans Immunity, Mucosal Interferon-gamma/metabolism Interleukin-12/metabolism Interleukin-15/metabolism Intestinal Mucosa/immunology Lymphocyte Subsets/immunology Lymphocytes/immunology Mice Mice, Inbred C57BL Mice, Knockout
Chemicals
Antibodies, Monoclonal CD40 Antigens Interleukin-15 Interleukin-12 Interferon-gamma
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Fuchs Anja
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Vermi William
Lee Jacob S
Lonardi Silvia
Gilfillan Susan
Newberry Rodney D
Cella Marina
Colonna Marco
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2013.02.010
Published
2013-04-18
Epub
2013-00-28
Pages
769-81
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC3634355
Subset
IM
Grants
NIDDK NIH HHS · P30DK052574 · United States
NIAID NIH HHS · U01 AI095542-01 · United States
NIDCR NIH HHS · R01 DE021255-01 · United States
NIAID NIH HHS · T32 AI007163 · United States
NIAID NIH HHS · U01 AI095542 · United States
NIDCR NIH HHS · R01 DE021255 · United States
NIDDK NIH HHS · R01 DK064798 · United States
NIDDK NIH HHS · R01DK064798 · United States
NIDDK NIH HHS · P30 DK052574 · United States
Corrections
CommentIn
PMID: 23601681
External Links
PubMed source DOI: 10.1016/j.immuni.2013.02.010 PMC Full Text View journal details
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