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P2Y 2 R deletion ameliorates sialadenitis in IL-14α-transgenic mice.
- Source :
-
Oral diseases [Oral Dis] 2018 Jul; Vol. 24 (5), pp. 761-771. Date of Electronic Publication: 2018 Mar 13. - Publication Year :
- 2018
-
Abstract
- Objective: Interleukin-14α-transgenic (IL-14αTG) mice develop an autoimmune exocrinopathy with characteristics similar to Sjögren's syndrome, including sialadenitis and hyposalivation. The P2Y <subscript>2</subscript> receptor (P2Y <subscript>2</subscript> 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 <subscript>2</subscript> Rs in autoimmune sialadenitis in the IL-14αTG mouse model of Sjögren's syndrome.<br />Materials and Methods: IL-14αTG mice were bred with P2Y <subscript>2</subscript> R <superscript>-/-</superscript> mice to generate IL-14αTG × P2Y <subscript>2</subscript> R <superscript>-/-</superscript> mice. P2Y <subscript>2</subscript> 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 <subscript>2</subscript> R <superscript>-/-</superscript> , and C57BL/6 control mice at 9 and 12 months of age.<br />Results: Genetic ablation of P2Y <subscript>2</subscript> 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 <subscript>2</subscript> R <superscript>-/-</superscript> mice. Decreased sialadenitis in IL-14αTG × P2Y <subscript>2</subscript> R <superscript>-/-</superscript> mice correlated with decreased lymphotoxin-α levels, a critical proinflammatory cytokine associated with autoimmune pathology in IL-14αTG mice.<br />Conclusions: The results of this study suggest that P2Y <subscript>2</subscript> Rs contribute to the development of salivary gland inflammation in IL-14αTG mice and may also contribute to autoimmune sialadenitis in humans.<br /> (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)
- Subjects :
- Animals
Calcium metabolism
Cells, Cultured
Disease Models, Animal
Epithelial Cells
Female
Gene Expression
Interleukins genetics
Lymphocyte Count
Lymphotoxin-alpha metabolism
Mice
Mice, Knockout
Saliva metabolism
Sjogren's Syndrome genetics
Submandibular Gland metabolism
Submandibular Gland pathology
Uridine Triphosphate pharmacology
Vesicular Transport Proteins
B-Lymphocytes
Receptors, Purinergic P2Y2 genetics
Receptors, Purinergic P2Y2 metabolism
Sialadenitis genetics
T-Lymphocytes
Subjects
Details
- Language :
- English
- ISSN :
- 1601-0825
- Volume :
- 24
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Oral diseases
- Publication Type :
- Academic Journal
- Accession number :
- 29297959
- Full Text :
- https://doi.org/10.1111/odi.12823