P2Y 2 R deletion ameliorates sialadenitis in IL-14α-transgenic mice

• Published in: Oral diseases Vol. 24; no. 5; pp. 761 - 771
• Main Authors: Woods, L T, Camden, J M, Khalafalla, M G, Petris, M J, Erb, L, Ambrus, Jr, J L, Weisman, G A
• Format: Journal Article
• Language: English
• Published: Denmark 01.07.2018
• Subjects: Animals; B-Lymphocytes; Calcium - metabolism; Cells, Cultured; Disease Models, Animal; Epithelial Cells; Female; Gene Expression; Interleukins - genetics; Lymphocyte Count; Lymphotoxin-alpha - metabolism; Mice; Mice, Knockout; Receptors, Purinergic P2Y2 - genetics; Receptors, Purinergic P2Y2 - metabolism; Saliva - metabolism; Sialadenitis - genetics; Sjogren's Syndrome - genetics; Submandibular Gland - metabolism; Submandibular Gland - pathology; T-Lymphocytes; Uridine Triphosphate - pharmacology; purinergic receptors; salivary glands; autoimmunity; Sjögren's syndrome; nucleotides; lymphotoxin-alpha
• ISSN: 1354-523X; 1601-0825
• DOI: 10.1111/odi.12823

Interleukin-14α-transgenic (IL-14αTG) mice develop an autoimmune exocrinopathy with characteristics similar to Sjögren's syndrome, including sialadenitis and hyposalivation. The P2Y receptor (P2Y 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 Rs in autoimmune sialadenitis in the IL-14αTG mouse model of Sjögren's syndrome. IL-14αTG mice were bred with P2Y R mice to generate IL-14αTG × P2Y R mice. P2Y 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 × P2Y R , and C57BL/6 control mice at 9 and 12 months of age. Genetic ablation of P2Y 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 × P2Y R mice. Decreased sialadenitis in IL-14αTG × P2Y 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 P2Y Rs contribute to the development of salivary gland inflammation in IL-14αTG mice and may also contribute to autoimmune sialadenitis in humans.