Cutting Edge: Dysregulated CARD9 Signaling in Neutrophils Drives Inflammation in a Mouse Model of Neutrophilic Dermatoses

Sarang Tartey; Prajwal Gurung; Parimal Samir; Amanda Burton; Thirumala-Devi Kanneganti

doi:10.4049/jimmunol.1800760

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Cutting Edge: Dysregulated CARD9 Signaling in Neutrophils Drives Inflammation in a Mouse Model of Neutrophilic Dermatoses

Journal article

Peer reviewed

Cutting Edge: Dysregulated CARD9 Signaling in Neutrophils Drives Inflammation in a Mouse Model of Neutrophilic Dermatoses

Sarang Tartey, Prajwal Gurung, Parimal Samir, Amanda Burton and Thirumala-Devi Kanneganti

The Journal of immunology (1950), Vol.201(6), pp.1639-1644

09/15/2018

DOI: 10.4049/jimmunol.1800760

PMCID: PMC6483079

PMID: 30082320

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Abstract

Mice homozygous for the Y208N amino acid substitution in the carboxy terminus of SHP-1 (referred to as mice) spontaneously develop a severe inflammatory disease resembling neutrophilic dermatosis in humans. Disease in mice is characterized by persistent footpad swelling and suppurative inflammation. Recently, in addition to IL-1α and IL-1R signaling, we demonstrated a pivotal role for RIPK1, TAK1, and ASK1 in promoting inflammatory disease in mice. In the current study we have identified a previously unknown role for CARD9 signaling as a critical regulator for -mediated footpad inflammation. Genetic deletion of CARD9 significantly rescued the -mediated footpad inflammation. Mechanistically, enhanced IL-1α-mediated signaling in mice neutrophils was dampened in mice. Collectively, this study identifies SHP-1 and CARD9 cross-talk as a novel regulator of IL-1α-driven inflammation and opens future avenues for finding novel drug targets to treat neutrophilic dermatosis in humans.

CARD Signaling Adaptor Proteins - immunology

Inflammation - pathology

Protein Tyrosine Phosphatase, Non-Receptor Type 6 - immunology

Interleukin-1alpha - immunology

Dermatitis - genetics

Dermatitis - immunology

Receptors, Interleukin-1 - immunology

Receptors, Interleukin-1 - genetics

Neutrophils - immunology

Inflammation - immunology

Signal Transduction - genetics

Mutation, Missense

Protein Tyrosine Phosphatase, Non-Receptor Type 6 - genetics

CARD Signaling Adaptor Proteins - genetics

Mice, Knockout

Dermatitis - pathology

Signal Transduction - immunology

Animals

Inflammation - genetics

Interleukin-1alpha - genetics

Mice

Amino Acid Substitution

Disease Models, Animal

Neutrophils - pathology

Details

Title: Subtitle: Cutting Edge: Dysregulated CARD9 Signaling in Neutrophils Drives Inflammation in a Mouse Model of Neutrophilic Dermatoses
Creators: Sarang Tartey - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105; and
Prajwal Gurung - Inflammation Program, University of Iowa, Iowa City, IA 52241
Parimal Samir - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105; and
Amanda Burton - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105; and
Thirumala-Devi Kanneganti - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105; and Thirumala-Devi.Kanneganti@StJude.org
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.201(6), pp.1639-1644
DOI: 10.4049/jimmunol.1800760
PMID: 30082320
PMCID: PMC6483079
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: R01 AI101935 / NIAID NIH HHS P30 CA021765 / NCI NIH HHS R01 AR056296 / NIAMS NIH HHS R37 AI101935 / NIAID NIH HHS R01 CA163507 / NCI NIH HHS R01 AI124346 / NIAID NIH HHS
Language: English
Date published: 09/15/2018
Academic Unit: Infectious Diseases; Internal Medicine
Record Identifier: 9984094528402771

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