Tissue-specific activation of Myd88-dependent pathways governs disease severity in primary Sjögren's syndrome

Jeremy Kiripolsky, Eileen M. Kasperek, Chengsong Zhu, Quan Zhen Li, Jia Wang, Guan Yu, Jill M. Kramer

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Myd88 activation is an important driver of autoimmunity. Primary Sjögren'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.

Original languageEnglish (US)
Article number102608
JournalJournal of Autoimmunity
Volume118
DOIs
StatePublished - Mar 2021

Keywords

  • Anti-nuclear antibody
  • Autoimmunity
  • B cell
  • Exocrine gland
  • Saliva
  • Sialadenitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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