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P2Y2 R deletion ameliorates sialadenitis in IL-14?-transgenic mice.

ABSTRACT: OBJECTIVE:Interleukin-14?-transgenic (IL-14?TG) mice develop an autoimmune exocrinopathy with characteristics similar to Sjögren's syndrome, including sialadenitis and hyposalivation. The P2Y2 receptor (P2Y2 R) for extracellular ATP and UTP is upregulated during salivary gland inflammation (i.e., sialadenitis) where it regulates numerous inflammatory responses. This study investigated the role of P2Y2 Rs in autoimmune sialadenitis in the IL-14?TG mouse model of Sjögren's syndrome. MATERIALS AND METHODS:IL-14?TG mice were bred with P2Y2 R-/- mice to generate IL-14?TG × P2Y2 R-/- mice. P2Y2 R expression, lymphocytic focus scores, B- and T-cell accumulation, and lymphotoxin-? expression were evaluated in the submandibular glands (SMG) along with carbachol-stimulated saliva secretion in IL-14?TG, IL-14?TG × P2Y2 R-/- , and C57BL/6 control mice at 9 and 12 months of age. RESULTS:Genetic ablation of P2Y2 Rs in IL-14?TG mice significantly reduced B and T lymphocyte infiltration of SMGs. However, reduced sialadenitis did not restore saliva secretion in IL-14?TG × P2Y2 R-/- mice. Decreased sialadenitis in IL-14?TG × P2Y2 R-/- mice correlated with decreased lymphotoxin-? levels, a critical proinflammatory cytokine associated with autoimmune pathology in IL-14?TG mice. CONCLUSIONS:The results of this study suggest that P2Y2 Rs contribute to the development of salivary gland inflammation in IL-14?TG mice and may also contribute to autoimmune sialadenitis in humans.

SUBMITTER: Woods LT

PROVIDER: S-EPMC6644053 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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P2Y<sub>2</sub> R deletion ameliorates sialadenitis in IL-14α-transgenic mice.

Woods L T LT Camden J M JM Khalafalla M G MG Petris M J MJ Erb L L Ambrus J L JL Weisman G A GA

Oral diseases 20180313 5

<h4>Objective</h4>Interleukin-14α-transgenic (IL-14αTG) mice develop an autoimmune exocrinopathy with characteristics similar to Sjögren's syndrome, including sialadenitis and hyposalivation. The P2Y<sub>2</sub> receptor (P2Y<sub>2</sub> R) for extracellular ATP and UTP is upregulated during salivary gland inflammation (i.e., sialadenitis) where it regulates numerous inflammatory responses. This study investigated the role of P2Y<sub>2</sub> Rs in autoimmune sialadenitis in the IL-14αTG mouse mo ...[more]

PMID: 29297959

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Dataset Information

P2Y2 R deletion ameliorates sialadenitis in IL-14?-transgenic mice.

Publications

P2Y<sub>2</sub> R deletion ameliorates sialadenitis in IL-14α-transgenic mice.

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