NLRP10 is a NOD-like receptor essential to initiate adaptive immunity by dendritic cells

Stephanie C. Eisenbarth; Adam Williams; Oscar R. Colegio; Hailong Meng; Till Strowig; Anthony Rongvaux; Jorge Henao-Mejia; Christoph A. Thaiss; Sophie Joly; David G. Gonzalez; Lan Xu; Lauren A. Zenewicz; Ann M. Haberman; Eran Elinav; Steven H. Kleinstein; Fayyaz S. Sutterwala; Richard A. Flavell

doi:10.1038/nature11012

NLRP10 is a NOD-like receptor essential to initiate adaptive immunity by dendritic cells

Stephanie C. Eisenbarth^*, Adam Williams, Oscar R. Colegio, Hailong Meng, Till Strowig, Anthony Rongvaux, Jorge Henao-Mejia, Christoph A. Thaiss, Sophie Joly, David G. Gonzalez, Lan Xu, Lauren A. Zenewicz, Ann M. Haberman, Eran Elinav, Steven H. Kleinstein, Fayyaz S. Sutterwala, Richard A. Flavell

^*Corresponding author for this work

Medicine, Allergy Division

Research output: Contribution to journal › Article › peer-review

118 Scopus citations

Abstract

NLRs (nucleotide-binding domain leucine-rich-repeat-containing receptors; NOD-like receptors) are a class of pattern recognition receptor (PRR) that respond to host perturbation from either infectious agents or cellular stress. The function of most NLR family members has not been characterized and their role in instructing adaptive immune responses remains unclear. NLRP10 (also known as PYNOD, NALP10, PAN5 and NOD8) is the only NLR lacking the putative ligand-binding leucine-rich-repeat domain, and has been postulated to be a negative regulator of other NLR members, including NLRP3 (refs 4-6). We did not find evidence that NLRP10 functions through an inflammasome to regulate caspase-1 activity nor that it regulates other inflammasomes. Instead, Nlrp10 ^-/- mice had a profound defect in helper T-cell-driven immune responses to a diverse array of adjuvants, including lipopolysaccharide, aluminium hydroxide and complete Freund's adjuvant. Adaptive immunity was impaired in the absence of NLRP10 because of a dendritic cell (DC) intrinsic defect in emigration from inflamed tissues, whereas upregulation of DC costimulatory molecules and chemotaxis to CCR7-dependent and-independent ligands remained intact. The loss of antigen transport to the draining lymph nodes by a subset of migratory DCs resulted in an almost absolute loss in naive CD4 ⁺ T-cell priming, highlighting the critical link between diverse innate immune stimulation, NLRP10 activity and the immune function of mature DCs.

Original language	English (US)
Pages (from-to)	510-513
Number of pages	4
Journal	Nature
Volume	484
Issue number	7395
DOIs	https://doi.org/10.1038/nature11012
State	Published - Apr 26 2012

Funding

Acknowledgements We would like to thank R. Medzhitov and M. Albert for discussion and review of this manuscript, and F. Duffy for assistance with manuscript preparation. S.C.E. was supported by T32HL007974, K08AI085038 and Yale CTSA (UL1 RR024139).O.R.C. was supported bythe Damon RunyonCancer ResearchFoundation (DRG 108-09), the Yale CTSA (UL1 RR024139 and 5KL2RR024138), the Yale SPORE in Skin Cancer (1 P50 CA121974) and the Dermatology Foundation. E.E. is supported by Cancer Research Institute, the American Physicians for Medicine in Israel Foundation, and the United States-Israel binational Foundation grant. A.M.H., D.G.G. and in vivo imaging were supported by Yale Rheumatologic Disease Research Core Center P30AR053495. F.S.S. was supported by R01AI087630 and an Edward Mallinckrodt,Jr.Foundationscholarship. A.W. was a Howard Hughes fellow andR.A.F. is an Investigator of the Howard Hughes Medical Institute.

ASJC Scopus subject areas

General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/nature11012

Cite this

Eisenbarth, S. C., Williams, A., Colegio, O. R., Meng, H., Strowig, T., Rongvaux, A., Henao-Mejia, J., Thaiss, C. A., Joly, S., Gonzalez, D. G., Xu, L., Zenewicz, L. A., Haberman, A. M., Elinav, E., Kleinstein, S. H., Sutterwala, F. S., & Flavell, R. A. (2012). NLRP10 is a NOD-like receptor essential to initiate adaptive immunity by dendritic cells. Nature, 484(7395), 510-513. https://doi.org/10.1038/nature11012

@article{3b442ef9573045b9981d723a7fad42ea,

title = "NLRP10 is a NOD-like receptor essential to initiate adaptive immunity by dendritic cells",

abstract = " NLRs (nucleotide-binding domain leucine-rich-repeat-containing receptors; NOD-like receptors) are a class of pattern recognition receptor (PRR) that respond to host perturbation from either infectious agents or cellular stress. The function of most NLR family members has not been characterized and their role in instructing adaptive immune responses remains unclear. NLRP10 (also known as PYNOD, NALP10, PAN5 and NOD8) is the only NLR lacking the putative ligand-binding leucine-rich-repeat domain, and has been postulated to be a negative regulator of other NLR members, including NLRP3 (refs 4-6). We did not find evidence that NLRP10 functions through an inflammasome to regulate caspase-1 activity nor that it regulates other inflammasomes. Instead, Nlrp10 -/- mice had a profound defect in helper T-cell-driven immune responses to a diverse array of adjuvants, including lipopolysaccharide, aluminium hydroxide and complete Freund's adjuvant. Adaptive immunity was impaired in the absence of NLRP10 because of a dendritic cell (DC) intrinsic defect in emigration from inflamed tissues, whereas upregulation of DC costimulatory molecules and chemotaxis to CCR7-dependent and-independent ligands remained intact. The loss of antigen transport to the draining lymph nodes by a subset of migratory DCs resulted in an almost absolute loss in naive CD4 + T-cell priming, highlighting the critical link between diverse innate immune stimulation, NLRP10 activity and the immune function of mature DCs.",

author = "Eisenbarth, {Stephanie C.} and Adam Williams and Colegio, {Oscar R.} and Hailong Meng and Till Strowig and Anthony Rongvaux and Jorge Henao-Mejia and Thaiss, {Christoph A.} and Sophie Joly and Gonzalez, {David G.} and Lan Xu and Zenewicz, {Lauren A.} and Haberman, {Ann M.} and Eran Elinav and Kleinstein, {Steven H.} and Sutterwala, {Fayyaz S.} and Flavell, {Richard A.}",

note = "Funding Information: Acknowledgements We would like to thank R. Medzhitov and M. Albert for discussion and review of this manuscript, and F. Duffy for assistance with manuscript preparation. S.C.E. was supported by T32HL007974, K08AI085038 and Yale CTSA (UL1 RR024139).O.R.C. was supported bythe Damon RunyonCancer ResearchFoundation (DRG 108-09), the Yale CTSA (UL1 RR024139 and 5KL2RR024138), the Yale SPORE in Skin Cancer (1 P50 CA121974) and the Dermatology Foundation. E.E. is supported by Cancer Research Institute, the American Physicians for Medicine in Israel Foundation, and the United States-Israel binational Foundation grant. A.M.H., D.G.G. and in vivo imaging were supported by Yale Rheumatologic Disease Research Core Center P30AR053495. F.S.S. was supported by R01AI087630 and an Edward Mallinckrodt,Jr.Foundationscholarship. A.W. was a Howard Hughes fellow andR.A.F. is an Investigator of the Howard Hughes Medical Institute.",

year = "2012",

month = apr,

day = "26",

doi = "10.1038/nature11012",

language = "English (US)",

volume = "484",

pages = "510--513",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "7395",

}

Eisenbarth, SC , Williams, A, Colegio, OR, Meng, H, Strowig, T, Rongvaux, A, Henao-Mejia, J, Thaiss, CA, Joly, S, Gonzalez, DG, Xu, L, Zenewicz, LA, Haberman, AM, Elinav, E, Kleinstein, SH, Sutterwala, FS & Flavell, RA 2012, 'NLRP10 is a NOD-like receptor essential to initiate adaptive immunity by dendritic cells', Nature, vol. 484, no. 7395, pp. 510-513. https://doi.org/10.1038/nature11012

TY - JOUR

T1 - NLRP10 is a NOD-like receptor essential to initiate adaptive immunity by dendritic cells

AU - Eisenbarth, Stephanie C.

AU - Williams, Adam

AU - Colegio, Oscar R.

AU - Meng, Hailong

AU - Strowig, Till

AU - Rongvaux, Anthony

AU - Henao-Mejia, Jorge

AU - Thaiss, Christoph A.

AU - Joly, Sophie

AU - Gonzalez, David G.

AU - Xu, Lan

AU - Zenewicz, Lauren A.

AU - Haberman, Ann M.

AU - Elinav, Eran

AU - Kleinstein, Steven H.

AU - Sutterwala, Fayyaz S.

AU - Flavell, Richard A.

N1 - Funding Information: Acknowledgements We would like to thank R. Medzhitov and M. Albert for discussion and review of this manuscript, and F. Duffy for assistance with manuscript preparation. S.C.E. was supported by T32HL007974, K08AI085038 and Yale CTSA (UL1 RR024139).O.R.C. was supported bythe Damon RunyonCancer ResearchFoundation (DRG 108-09), the Yale CTSA (UL1 RR024139 and 5KL2RR024138), the Yale SPORE in Skin Cancer (1 P50 CA121974) and the Dermatology Foundation. E.E. is supported by Cancer Research Institute, the American Physicians for Medicine in Israel Foundation, and the United States-Israel binational Foundation grant. A.M.H., D.G.G. and in vivo imaging were supported by Yale Rheumatologic Disease Research Core Center P30AR053495. F.S.S. was supported by R01AI087630 and an Edward Mallinckrodt,Jr.Foundationscholarship. A.W. was a Howard Hughes fellow andR.A.F. is an Investigator of the Howard Hughes Medical Institute.

PY - 2012/4/26

Y1 - 2012/4/26

N2 - NLRs (nucleotide-binding domain leucine-rich-repeat-containing receptors; NOD-like receptors) are a class of pattern recognition receptor (PRR) that respond to host perturbation from either infectious agents or cellular stress. The function of most NLR family members has not been characterized and their role in instructing adaptive immune responses remains unclear. NLRP10 (also known as PYNOD, NALP10, PAN5 and NOD8) is the only NLR lacking the putative ligand-binding leucine-rich-repeat domain, and has been postulated to be a negative regulator of other NLR members, including NLRP3 (refs 4-6). We did not find evidence that NLRP10 functions through an inflammasome to regulate caspase-1 activity nor that it regulates other inflammasomes. Instead, Nlrp10 -/- mice had a profound defect in helper T-cell-driven immune responses to a diverse array of adjuvants, including lipopolysaccharide, aluminium hydroxide and complete Freund's adjuvant. Adaptive immunity was impaired in the absence of NLRP10 because of a dendritic cell (DC) intrinsic defect in emigration from inflamed tissues, whereas upregulation of DC costimulatory molecules and chemotaxis to CCR7-dependent and-independent ligands remained intact. The loss of antigen transport to the draining lymph nodes by a subset of migratory DCs resulted in an almost absolute loss in naive CD4 + T-cell priming, highlighting the critical link between diverse innate immune stimulation, NLRP10 activity and the immune function of mature DCs.

AB - NLRs (nucleotide-binding domain leucine-rich-repeat-containing receptors; NOD-like receptors) are a class of pattern recognition receptor (PRR) that respond to host perturbation from either infectious agents or cellular stress. The function of most NLR family members has not been characterized and their role in instructing adaptive immune responses remains unclear. NLRP10 (also known as PYNOD, NALP10, PAN5 and NOD8) is the only NLR lacking the putative ligand-binding leucine-rich-repeat domain, and has been postulated to be a negative regulator of other NLR members, including NLRP3 (refs 4-6). We did not find evidence that NLRP10 functions through an inflammasome to regulate caspase-1 activity nor that it regulates other inflammasomes. Instead, Nlrp10 -/- mice had a profound defect in helper T-cell-driven immune responses to a diverse array of adjuvants, including lipopolysaccharide, aluminium hydroxide and complete Freund's adjuvant. Adaptive immunity was impaired in the absence of NLRP10 because of a dendritic cell (DC) intrinsic defect in emigration from inflamed tissues, whereas upregulation of DC costimulatory molecules and chemotaxis to CCR7-dependent and-independent ligands remained intact. The loss of antigen transport to the draining lymph nodes by a subset of migratory DCs resulted in an almost absolute loss in naive CD4 + T-cell priming, highlighting the critical link between diverse innate immune stimulation, NLRP10 activity and the immune function of mature DCs.

UR - http://www.scopus.com/inward/record.url?scp=84860233490&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860233490&partnerID=8YFLogxK

U2 - 10.1038/nature11012

DO - 10.1038/nature11012

M3 - Article

C2 - 22538615

AN - SCOPUS:84860233490

SN - 0028-0836

VL - 484

SP - 510

EP - 513

JO - Nature

JF - Nature

IS - 7395

ER -

NLRP10 is a NOD-like receptor essential to initiate adaptive immunity by dendritic cells

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this