Innate immune adaptor MyD88 deficiency prevents skin inflammation in SHARPIN-deficient mice

Bhesh Raj Sharma; Rajendra Karki; Ein Lee; Qifan Zhu; Prajwal Gurung; Thirumala-Devi Kanneganti

doi:10.1038/s41418-018-0159-7

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Innate immune adaptor MyD88 deficiency prevents skin inflammation in SHARPIN-deficient mice

Journal article

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Innate immune adaptor MyD88 deficiency prevents skin inflammation in SHARPIN-deficient mice

Bhesh Raj Sharma, Rajendra Karki, Ein Lee, Qifan Zhu, Prajwal Gurung and Thirumala-Devi Kanneganti

Cell death and differentiation, Vol.26(4), pp.741-750

03/2019

DOI: 10.1038/s41418-018-0159-7

PMCID: PMC6460383

PMID: 30038386

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Abstract

Mice deficient in SHANK-associated RH domain-interacting protein (SHARPIN), a component of the linear ubiquitin chain assembly complex (LUBAC), develop a spontaneous inflammatory disorder with pathologic hallmarks similar to atopic dermatitis and psoriasis in humans. Previous studies identified the crucial role of components of the TNF and IL-1 signaling pathways in the progression of disease in SHARPIN-deficient mice. However, an innate immune adaptor or sensor that relates to the disease progression has remained unknown. In this study, we found that the genetic ablation of myeloid differentiation primary response 88 (MyD88) completely rescued skin inflammation in SHARPIN-deficient (Sharpin ) mice. Systemic inflammation and immune cell dysregulation were partially rescued. Fibroblasts derived from Sharpin Myd88 mice failed to provide protection against TNF-induced cell death. Sharpin Myd88 mice had reduced TNF production in their skin. Furthermore, depletion of the microbiota through the oral administration of antibiotics (ABX) partially rescued both the skin inflammation and systemic inflammation, demonstrating a role for the gut microbiota in SHARPIN-deficient mice. Our findings suggest a detrimental role for the innate immune adaptor MyD88 in instigating skin inflammation in Sharpin mice.

Details

Title: Subtitle: Innate immune adaptor MyD88 deficiency prevents skin inflammation in SHARPIN-deficient mice
Creators: Bhesh Raj Sharma - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA
Rajendra Karki - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA
Ein Lee - Integrated Biomedical Sciences Program, University of Tennessee Health Science Center, Memphis, TN, 38163, USA
Qifan Zhu - Integrated Biomedical Sciences Program, University of Tennessee Health Science Center, Memphis, TN, 38163, USA
Prajwal Gurung - Inflammation Program, University of Iowa, Iowa City, IA, USA
Thirumala-Devi Kanneganti - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA. thirumala-devi.kanneganti@stjude.org
Resource Type: Journal article
Publication Details: Cell death and differentiation, Vol.26(4), pp.741-750
DOI: 10.1038/s41418-018-0159-7
PMID: 30038386
PMCID: PMC6460383
NLM abbreviation: Cell Death Differ
ISSN: 1350-9047
eISSN: 1476-5403
Grant note: R01 AI101935 / NIAID 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: 03/2019
Academic Unit: Infectious Diseases; Internal Medicine
Record Identifier: 9984094579502771

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