Dysregulated co-stimulatory molecule expression in a Sjögren's syndrome mouse model with potential implications by microRNA-146a.
Sjögren's syndrome (SjS) is an autoimmune condition that primarily affects salivary and lacrimal glands, causing loss of secretion. We have previously shown that microRNA-146a (miR-146a) is over-expressed in the salivary glands and peripheral blood mononuclear cells (PBMC) of SjS-prone mice (C57BL/6.NOD-Aec1Aec2, B6DC) and in PBMC of SjS patients. The purpose of this research was to identify a target molecule of miR-146a and identify subpopulations of cells affected by altered miR-146a in the salivary glands of SjS-prone mice. In silico analyses identified costimulatory molecule CD80 as a potential target of miR-146a. Luciferase assay of the human CD80 3'untranslated region demonstrated miR-146a directly inhibited CD80 protein expression as indicated by reduced luciferase reporter expression and an examination of B6DC salivary glands revealed a reduction in CD80 protein. More interestingly, the specific reduction in CD80 protein was detected from the salivary gland epithelial cell population and in interstitial dendritic cells in the glands as well. The reduction in CD80 protein levels in salivary gland epithelial cells were negatively associated with elevated miR-146a expression. Therefore, this study provides the first indication that salivary gland epithelial cells may be critically involved in SjS progression by altering CD86:CD80 protein ratio in response to miR-146a upregulation.
Departments of Oral and Maxillofacial Diagnostic Sciences and Oral Biology, University of Florida College of Dentistry, 1395 Center Drive, Gainesville, FL 32610, USA. Electronic address: agauna@dental.ufl.edu.
Adrienne E
AE
Gauna
Departments of Oral and Maxillofacial Diagnostic Sciences and Oral Biology, University of Florida College of Dentistry, 1395 Center Drive, Gainesville, FL 32610, USA. Electronic address: yjpark@ufl.edu.
Yun-Jong
YJ
Park
Departments of Oral and Maxillofacial Diagnostic Sciences and Oral Biology, University of Florida College of Dentistry, 1395 Center Drive, Gainesville, FL 32610, USA. Electronic address: gnayar33@gmail.com.
Gautam
G
Nayar
Departments of Oral and Maxillofacial Diagnostic Sciences and Oral Biology, University of Florida College of Dentistry, 1395 Center Drive, Gainesville, FL 32610, USA. Electronic address: Monate@dental.ufl.edu.
Marelys
M
Onate
Department of Immunology and Infectious Disease, The Forsyth Institute, 245 First Street, Cambridge, MA 2142, USA. Electronic address: Junojin1@gmail.com.
Jun-o
JO
Jin
Departments of Oral and Maxillofacial Diagnostic Sciences and Oral Biology, University of Florida College of Dentistry, 1395 Center Drive, Gainesville, FL 32610, USA. Electronic address: cstewart@dental.ufl.edu.
Carol M
CM
Stewart
Department of Immunology and Infectious Disease, The Forsyth Institute, 245 First Street, Cambridge, MA 2142, USA. Electronic address: QYu@forsyth.org.
Qing
Q
Yu
Departments of Oral and Maxillofacial Diagnostic Sciences and Oral Biology, University of Florida College of Dentistry, 1395 Center Drive, Gainesville, FL 32610, USA. Electronic address: scha@dental.ufl.edu.
Seunghee
S
Cha
D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D051940:B7-2 Antigen / Q000096:biosynthesis* / Q000276:immunology; D015153:Blotting, Western; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000276:immunology; D016133:Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000276:immunology; D014162:Transfection; D015854:Up-Regulation
D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D035683:MicroRNAs; C534190:Mirn146 microRNA, mouse
CD80; Co-stimulation; Epithelial cells; Salivary glands; Sjögren’s syndrome; miR-146a; microRNA