STIM1 and STIM2 protein deficiency in T lymphocytes underlies development of the exocrine gland autoimmune disease, Sjögren's syndrome

Kwong Tai Cheng, Ilias Alevizos, Xibao Liu, Wiliam D. Swaim, Hongen Yin, Stefan Feske, Masatsugu Oh-hora, Indu S. Ambudkar

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54 Citations (Scopus)

Abstract

Primary Sjögren's Syndrome (pSS) is an autoimmune disease involving salivary and other exocrine glands that leads to progressive lymphocytic infiltration into the gland, tissue damage, and secretory defects. The mechanism underlying this disease remains poorly understood. Here we report that mice with T-cell-targeted deletion of Stromal Interaction Molecule (STIM) 1 and STIM2 [double-knockout (DKO)] mice develop spontaneous and severe pSS-like autoimmune disease, displaying major hallmarks of the disease. In DKO mice, diffuse lymphocytic infiltration was seen in submandibular glands, a major target of pSS, by age 6 wk, progressing to severe inflammation by age 12 wk. Sjögren's syndrome-specific autoantibodies (SSA/Ro and SSB/La) were detected in the serum, and progressive salivary gland destruction and loss of fluid secretion were also seen. Importantly, we report that peripheral blood mononuclear cells as well as lymphocytic infiltrates in submandibular glands from patients with pSS demonstrated significant reductions in STIM1 and STIM2 proteins. Store-operated calcium entry was also reduced in peripheral blood mononuclear cells from pSS patients compared with those fromhealthy controls. Thus, deficiency of STIM1 and STIM2 proteins in T cells, and consequent defects in Ca2+ signaling, are associated with salivary gland autoimmunopathy in DKO mice and pSS patients. These data reveal a previously unreported link between STIM1 and STIM2 proteins and pSS.

Original languageEnglish
Pages (from-to)14544-14549
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number36
DOIs
Publication statusPublished - Sept 4 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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