P2Y₂ R deletion ameliorates sialadenitis in IL-14α-transgenic mice

Interleukin-14α-transgenic (IL-14αTG) 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-14αTG mouse model of Sjögren's syndrome.

IL-14αTG mice were bred with P2Y₂ R^-/- mice to generate IL-14αTG × P2Y₂ R^-/- mice. P2Y₂ R expression, lymphocytic focus scores, B- and T-cell accumulation, and lymphotoxin-α expression were evaluated in the submandibular glands (SMG) along with carbachol-stimulated saliva secretion in IL-14αTG, IL-14αTG × P2Y₂ R^-/- , and C57BL/6 control mice at 9 and 12 months of age.

Genetic ablation of P2Y₂ Rs in IL-14αTG mice significantly reduced B and T lymphocyte infiltration of SMGs. However, reduced sialadenitis did not restore saliva secretion in IL-14αTG × P2Y₂ R^-/- mice. Decreased sialadenitis in IL-14αTG × P2Y₂ R^-/- mice correlated with decreased lymphotoxin-α levels, a critical proinflammatory cytokine associated with autoimmune pathology in IL-14αTG mice.

The results of this study suggest that P2Y₂ Rs contribute to the development of salivary gland inflammation in IL-14αTG mice and may also contribute to autoimmune sialadenitis in humans.