Gene Expression Profiling of Lacrimal Glands Identifies the Ectopic Expression of MHC II on Glandular Cells As a Presymptomatic Feature in a Mouse Model of Primary Sjögren's Syndrome

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2018 Nov 16

PMID 30429844

Citations 5

Authors

Junping Yin

Junfeng Zheng

Fengyuan Deng

Wenjie Zhao

Yan Chen

Qiaoniang Huang

Renliang Huang

Lifang Wen

Xiaoyang Yue

Frank Petersen

Xinhua Yu

Affiliations

Soon will be listed here.

Abstract

Ectopic expression of MHC II molecules on glandular cells is a feature of primary Sjögren's syndrome (pSS). However, the cause of this ectopic expression and its potential role in the pathogenesis of the disease remains elusive. Here, we report that ectopic expression of MHC II molecules on glandular cells represents an early presymptomatic event in a mouse model of pSS induced by immunization of Ro60_316-335 peptide emulsified in TiterMax® as an adjuvant. Ectopic expression of MHC II was induced by TiterMax® but not by complete freund's adjuvant (CFA). Furthermore, immunization with Ro60_316-335 peptide emulsified in TiterMax®, but not in CFA, induced a pSS-like disease in mice. Our results suggests that ectopic expression of MHC II molecules on glandular cells represents a presymptomatic feature of pSS and that such ectopic expression can be induced by exogenous factors. In addition, this study also provides a novel mechanism how adjuvants can amplify immune responses.

Citing Articles

Ro60-Roles in RNA Processing, Inflammation, and Rheumatic Autoimmune Diseases.

Mahla R, Jones E, Dustin L Int J Mol Sci. 2024; 25(14).

PMID: 39062948 PMC: 11277228. DOI: 10.3390/ijms25147705.

Uncovering potential new biomarkers and immune infiltration characteristics in primary Sjögren's syndrome by integrated bioinformatics analysis.

Zhang N, Ji C, Bao X, Peng X, Tang M, Yuan C Medicine (Baltimore). 2023; 102(41):e35534.

PMID: 37832090 PMC: 10578719. DOI: 10.1097/MD.0000000000035534.

Lessons from Animal Models in Sjögren's Syndrome.

Mieliauskaite D, Kontenis V, Siaurys A Int J Mol Sci. 2023; 24(16).

PMID: 37629175 PMC: 10454747. DOI: 10.3390/ijms241612995.

Recent Advances in Mouse Models of Sjögren's Syndrome.

Gao Y, Chen Y, Zhang Z, Yu X, Zheng J Front Immunol. 2020; 11:1158.

PMID: 32695097 PMC: 7338666. DOI: 10.3389/fimmu.2020.01158.

Serum Levels of Autoantibodies Against Extracellular Antigens and Neutrophil Granule Proteins Increase in Patients with COPD Compared to Non-COPD Smokers.

Ma A, Wen L, Yin J, Hu Y, Yue X, Li J Int J Chron Obstruct Pulmon Dis. 2020; 15:189-200.

PMID: 32099344 PMC: 6996218. DOI: 10.2147/COPD.S235903.

References

Yu X, Petersen F . A methodological review of induced animal models of autoimmune diseases. Autoimmun Rev. 2018; 17(5):473-479. DOI: 10.1016/j.autrev.2018.03.001. View

Fox R . Sjögren's syndrome. Lancet. 2005; 366(9482):321-31. DOI: 10.1016/S0140-6736(05)66990-5. View

Lukic M, Mensah-Brown E, Galadari S, Shahin A . Lack of apoptosis of infiltrating cells as the mechanism of high susceptibility to EAE in DA rats. Dev Immunol. 2002; 8(3-4):193-200. PMC: 2276080. DOI: 10.1155/2001/32636. View

Shannon P, Markiel A, Ozier O, Baliga N, Wang J, Ramage D . Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003; 13(11):2498-504. PMC: 403769. DOI: 10.1101/gr.1239303. View

Steimle V, Siegrist C, Mottet A, MACH B . Regulation of MHC class II expression by interferon-gamma mediated by the transactivator gene CIITA. Science. 1994; 265(5168):106-9. DOI: 10.1126/science.8016643. View

Awate S, Babiuk L, Mutwiri G . Mechanisms of action of adjuvants. Front Immunol. 2013; 4:114. PMC: 3655441. DOI: 10.3389/fimmu.2013.00114. View

Rowe D, Griffiths M, Stewart J, Novick D, Beverley P, Isenberg D . HLA class I and II, interferon, interleukin 2, and the interleukin 2 receptor expression on labial biopsy specimens from patients with Sjögren's syndrome. Ann Rheum Dis. 1987; 46(8):580-6. PMC: 1002203. DOI: 10.1136/ard.46.8.580. View

Moutsopoulos H, Hooks J, Chan C, Dalavanga Y, Skopouli F, Detrick B . HLA-DR expression by labial minor salivary gland tissues in Sjögren's syndrome. Ann Rheum Dis. 1986; 45(8):677-83. PMC: 1001967. DOI: 10.1136/ard.45.8.677. View

Zheng J, Huang Q, Huang R, Deng F, Yue X, Yin J . B Cells Are Indispensable for a Novel Mouse Model of Primary Sjögren's Syndrome. Front Immunol. 2017; 8:1384. PMC: 5661054. DOI: 10.3389/fimmu.2017.01384. View

10.

Christodoulou M, Kapsogeorgou E, Moutsopoulos H . Characteristics of the minor salivary gland infiltrates in Sjögren's syndrome. J Autoimmun. 2009; 34(4):400-7. DOI: 10.1016/j.jaut.2009.10.004. View

11.

Turpie B, Yoshimura T, Gulati A, Rios J, Dartt D, Masli S . Sjögren's syndrome-like ocular surface disease in thrombospondin-1 deficient mice. Am J Pathol. 2009; 175(3):1136-47. PMC: 2731132. DOI: 10.2353/ajpath.2009.081058. View

12.

Lindahl G, Hedfors E, Klareskog L, Forsum U . Epithelial HLA-DR expression and T lymphocyte subsets in salivary glands in Sjögren's syndrome. Clin Exp Immunol. 1985; 61(3):475-82. PMC: 1577280. View

13.

Wakamatsu E, Matsumoto I, Yasukochi T, Naito Y, Goto D, Mamura M . Overexpression of phosphorylated STAT-1alpha in the labial salivary glands of patients with Sjögren's syndrome. Arthritis Rheum. 2006; 54(11):3476-84. DOI: 10.1002/art.22176. View

14.

Jonsson R, Theander E, Sjostrom B, Brokstad K, Henriksson G . Autoantibodies present before symptom onset in primary Sjögren syndrome. JAMA. 2013; 310(17):1854-5. DOI: 10.1001/jama.2013.278448. View

15.

Killedar S, Killedar S, Eckenrode S, McIndoe R, She J, Nguyen C . Early pathogenic events associated with Sjögren's syndrome (SjS)-like disease of the NOD mouse using microarray analysis. Lab Invest. 2006; 86(12):1243-60. DOI: 10.1038/labinvest.3700487. View

16.

Bennett B, Check I, Olsen M, Hunter R . A comparison of commercially available adjuvants for use in research. J Immunol Methods. 1992; 153(1-2):31-40. DOI: 10.1016/0022-1759(92)90302-a. View

17.

Nguyen C, Singson E, Kim J, Cornelius J, Attia R, Doyle M . Sjögren's syndrome-like disease of C57BL/6.NOD-Aec1 Aec2 mice: gender differences in keratoconjunctivitis sicca defined by a cross-over in the chromosome 3 Aec1 locus. Scand J Immunol. 2006; 64(3):295-307. DOI: 10.1111/j.1365-3083.2006.01828.x. View

18.

Hobart M, Ramassar V, Goes N, Urmson J, Halloran P . IFN regulatory factor-1 plays a central role in the regulation of the expression of class I and II MHC genes in vivo. J Immunol. 1997; 158(9):4260-9. View

19.

Harton J, Ting J . Class II transactivator: mastering the art of major histocompatibility complex expression. Mol Cell Biol. 2000; 20(17):6185-94. PMC: 86093. DOI: 10.1128/MCB.20.17.6185-6194.2000. View

20.

Billiau A, Matthys P . Modes of action of Freund's adjuvants in experimental models of autoimmune diseases. J Leukoc Biol. 2001; 70(6):849-60. View