@article{7c269595dafe460da59d74d56e367338,
title = "Tissue-specific activation of Myd88-dependent pathways governs disease severity in primary Sj{\"o}gren's syndrome",
abstract = "Myd88 activation is an important driver of autoimmunity. Primary Sj{\"o}gren's syndrome (pSS) is an autoimmune disease characterized by exocrine gland dysfunction in combination with serious systemic disease manifestations. Myd88-dependent signaling networks remain incompletely understood in the context of pSS. The objective of this study was to establish the contribution of tissue-specific Myd88 activation to local (exocrine) and systemic pSS manifestations. To this end, we generated two novel conditional knockout pSS mouse models; one lacking Myd88 in hematopoietic cells and a second strain in which Myd88 was deleted in the stromal compartment. Spontaneous production of inflammatory mediators was altered in salivary tissue, and nephritis was diminished in both conditional knockout strains. In contrast, pulmonary inflammation was increased in mice lacking Myd88 in hematopoietic cells and was reduced when Myd88 was ablated in stromal cells. Finally, anti-nuclear autoantibodies (ANAs) were attenuated in pSS mice lacking Myd88 in immune cells. Additionally, the ANA-specific B cell repertoire was skewed in the Myd88-deficient strains. Collectively, these data demonstrate that Myd88 activation in specific cell types is essential for distinct aspects of pSS pathology.",
keywords = "Anti-nuclear antibody, Autoimmunity, B cell, Exocrine gland, Saliva, Sialadenitis",
author = "Jeremy Kiripolsky and Kasperek, {Eileen M.} and Chengsong Zhu and Li, {Quan Zhen} and Jia Wang and Guan Yu and Kramer, {Jill M.}",
note = "Funding Information: The authors thank Dr. Terry D. Connell, Professor, Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, The University at Buffalo, State University of New York for critical review of the manuscript. Instrumentation for this work was provided by the Optical Imaging and Analysis Facility at the University of Buffalo. We thank Dr. Andrew McCall, Director of the Research Core Facility, for technical expertise. Funding for this work was provided by the NIH / National Institute of Dental and Craniofacial Research ( NIDCR ) [grant numbers F31DE02968 to JK and R01DE29472 to JMK]. Funding was also provided by the NIH / National Institute of Dental and Craniofacial Research ( NIDCR ) and Office of the Director , National Institutes of Health ( OD ) [grant number R56DE25218 ]. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health to the University at Buffalo [grant number UL1TR001412 ]. Additional support was provided by NIH / National Cancer Institute ( NCI ) to the Roswell Park Comprehensive Cancer Center Pathology Network Shared Resource [grant number P30CA016056 ]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = mar,
doi = "10.1016/j.jaut.2021.102608",
language = "English (US)",
volume = "118",
journal = "Journal of Autoimmunity",
issn = "0896-8411",
publisher = "Academic Press Inc.",
}