Cutting edge

AIM2 and endosomal TLRs differentially regulate arthritis and autoantibody production in DNase II-deficient mice

Rebecca Baum, Shruti Sharma, Susan Carpenter, Quan Zhen Li, Patricia Busto, Katherine A. Fitzgerald, Ann Marshak-Rothstein, Ellen M. Gravallese

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Innate immune pattern recognition receptors sense nucleic acids from microbes and orchestrate cytokine production to resolve infection. Inappropriate recognition of host nucleic acids also results in autoimmune disease. In this study, we use a model of inflammation resulting from accrual of self DNA (DNase II-/- type I IFN receptor [Ifnar]-/-) to understand the role of pattern recognition receptor-sensing pathways in arthritis and autoantibody production. Using triple knockout (TKO) mice deficient in DNase II/IFNaR together with deficiency in either stimulator of IFN genes (STING) or absent in melanoma 2 (AIM2), we reveal central roles for the STING and AIM2 pathways in arthritis. AIM2 TKO mice show limited inflammasome activation and, similar to STING TKO mice, have reduced inflammation in joints. Surprisingly, autoantibody production is maintained in AIM2 and STING TKO mice, whereas DNase II-/- Ifnar-/- mice also deficient in Unc93b, a chaperone required for TLR7/9 endosomal localization, fail to produce autoantibodies to nucleic acids. Collectively, these data support distinct roles for cytosolic and endosomal nucleic acid-sensing pathways in disease manifestations.

Original languageEnglish (US)
Pages (from-to)873-877
Number of pages5
JournalJournal of Immunology
Volume194
Issue number3
DOIs
StatePublished - Feb 1 2015

Fingerprint

Deoxyribonucleases
Knockout Mice
Autoantibodies
Nucleic Acids
Arthritis
Melanoma
Pattern Recognition Receptors
Gene Knockout Techniques
Inflammasomes
Inflammation
Deoxyribonuclease I
Genes
Autoimmune Diseases
Joints
Cytokines
DNA
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Cutting edge : AIM2 and endosomal TLRs differentially regulate arthritis and autoantibody production in DNase II-deficient mice. / Baum, Rebecca; Sharma, Shruti; Carpenter, Susan; Li, Quan Zhen; Busto, Patricia; Fitzgerald, Katherine A.; Marshak-Rothstein, Ann; Gravallese, Ellen M.

In: Journal of Immunology, Vol. 194, No. 3, 01.02.2015, p. 873-877.

Research output: Contribution to journalArticle

Baum, R, Sharma, S, Carpenter, S, Li, QZ, Busto, P, Fitzgerald, KA, Marshak-Rothstein, A & Gravallese, EM 2015, 'Cutting edge: AIM2 and endosomal TLRs differentially regulate arthritis and autoantibody production in DNase II-deficient mice', Journal of Immunology, vol. 194, no. 3, pp. 873-877. https://doi.org/10.4049/jimmunol.1402573
Baum, Rebecca ; Sharma, Shruti ; Carpenter, Susan ; Li, Quan Zhen ; Busto, Patricia ; Fitzgerald, Katherine A. ; Marshak-Rothstein, Ann ; Gravallese, Ellen M. / Cutting edge : AIM2 and endosomal TLRs differentially regulate arthritis and autoantibody production in DNase II-deficient mice. In: Journal of Immunology. 2015 ; Vol. 194, No. 3. pp. 873-877.
@article{16aaf2f129004f4e8d05c6f4b2f82fff,
title = "Cutting edge: AIM2 and endosomal TLRs differentially regulate arthritis and autoantibody production in DNase II-deficient mice",
abstract = "Innate immune pattern recognition receptors sense nucleic acids from microbes and orchestrate cytokine production to resolve infection. Inappropriate recognition of host nucleic acids also results in autoimmune disease. In this study, we use a model of inflammation resulting from accrual of self DNA (DNase II-/- type I IFN receptor [Ifnar]-/-) to understand the role of pattern recognition receptor-sensing pathways in arthritis and autoantibody production. Using triple knockout (TKO) mice deficient in DNase II/IFNaR together with deficiency in either stimulator of IFN genes (STING) or absent in melanoma 2 (AIM2), we reveal central roles for the STING and AIM2 pathways in arthritis. AIM2 TKO mice show limited inflammasome activation and, similar to STING TKO mice, have reduced inflammation in joints. Surprisingly, autoantibody production is maintained in AIM2 and STING TKO mice, whereas DNase II-/- Ifnar-/- mice also deficient in Unc93b, a chaperone required for TLR7/9 endosomal localization, fail to produce autoantibodies to nucleic acids. Collectively, these data support distinct roles for cytosolic and endosomal nucleic acid-sensing pathways in disease manifestations.",
author = "Rebecca Baum and Shruti Sharma and Susan Carpenter and Li, {Quan Zhen} and Patricia Busto and Fitzgerald, {Katherine A.} and Ann Marshak-Rothstein and Gravallese, {Ellen M.}",
year = "2015",
month = "2",
day = "1",
doi = "10.4049/jimmunol.1402573",
language = "English (US)",
volume = "194",
pages = "873--877",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - Cutting edge

T2 - AIM2 and endosomal TLRs differentially regulate arthritis and autoantibody production in DNase II-deficient mice

AU - Baum, Rebecca

AU - Sharma, Shruti

AU - Carpenter, Susan

AU - Li, Quan Zhen

AU - Busto, Patricia

AU - Fitzgerald, Katherine A.

AU - Marshak-Rothstein, Ann

AU - Gravallese, Ellen M.

PY - 2015/2/1

Y1 - 2015/2/1

N2 - Innate immune pattern recognition receptors sense nucleic acids from microbes and orchestrate cytokine production to resolve infection. Inappropriate recognition of host nucleic acids also results in autoimmune disease. In this study, we use a model of inflammation resulting from accrual of self DNA (DNase II-/- type I IFN receptor [Ifnar]-/-) to understand the role of pattern recognition receptor-sensing pathways in arthritis and autoantibody production. Using triple knockout (TKO) mice deficient in DNase II/IFNaR together with deficiency in either stimulator of IFN genes (STING) or absent in melanoma 2 (AIM2), we reveal central roles for the STING and AIM2 pathways in arthritis. AIM2 TKO mice show limited inflammasome activation and, similar to STING TKO mice, have reduced inflammation in joints. Surprisingly, autoantibody production is maintained in AIM2 and STING TKO mice, whereas DNase II-/- Ifnar-/- mice also deficient in Unc93b, a chaperone required for TLR7/9 endosomal localization, fail to produce autoantibodies to nucleic acids. Collectively, these data support distinct roles for cytosolic and endosomal nucleic acid-sensing pathways in disease manifestations.

AB - Innate immune pattern recognition receptors sense nucleic acids from microbes and orchestrate cytokine production to resolve infection. Inappropriate recognition of host nucleic acids also results in autoimmune disease. In this study, we use a model of inflammation resulting from accrual of self DNA (DNase II-/- type I IFN receptor [Ifnar]-/-) to understand the role of pattern recognition receptor-sensing pathways in arthritis and autoantibody production. Using triple knockout (TKO) mice deficient in DNase II/IFNaR together with deficiency in either stimulator of IFN genes (STING) or absent in melanoma 2 (AIM2), we reveal central roles for the STING and AIM2 pathways in arthritis. AIM2 TKO mice show limited inflammasome activation and, similar to STING TKO mice, have reduced inflammation in joints. Surprisingly, autoantibody production is maintained in AIM2 and STING TKO mice, whereas DNase II-/- Ifnar-/- mice also deficient in Unc93b, a chaperone required for TLR7/9 endosomal localization, fail to produce autoantibodies to nucleic acids. Collectively, these data support distinct roles for cytosolic and endosomal nucleic acid-sensing pathways in disease manifestations.

UR - http://www.scopus.com/inward/record.url?scp=84921478452&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84921478452&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1402573

DO - 10.4049/jimmunol.1402573

M3 - Article

VL - 194

SP - 873

EP - 877

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -