Sjogren's syndrome (SjS) is an autoimmune disease characterized primarily by exocrine gland dysfunction, specifically, the salivary and lacrimal glands. It can be systemic by affecting other organs including the Gl tract, skin, lungs, vasculature, kidneys, bladder and vagina. Involvement of the musculature can lead to flbromyalgla-llke symptoms and chronic fatigue. Approximately 20% of patients develop various neuropathies, including sensory, peripheral, cranial and myelopathic neuropathies exhibited by cognitive impairments such as dementia, lack of concentration, memory loss and various psychiatric disorders. As with many autoimmune connective tissue diseases, there exists a sexual dimorphism in SjS with women affected 10- to 20-times more frequently than men, suggesting a role for sex hormones in disease susceptibility or progression. A unique feature of SjS in both humans and animal models Is the formation of lymphocytic focus (LF) in the salivary and lacrimal glands. Although one of the more predominant cell populations infiltrating the glands is the pathogenic THI 7 cells that produce IL-17 and IL-22 cytokines, little is known about frequencies of infiltrating cells secreting these cytokines and the genetic profiles of their individual T cell receptors. Using a novel technology called microengraving designed for single cell analysis, this study aims to provide a proof of concept in examining individual TH17 cells that produce IL-22. To achieve this goal, two specific aims will be carried out: 1) characterizing individual IL-22-secretlng cells infiltrating the labial salivary glands (LSG) of SjS patients, and 2) identifying the T cell receptor (TCR)-P gene rearrangement of Individual IL-22 secreting cells in LSG of SjS patients. Results of the proposed study, therefore, will establish proof of concept for identification and characterization of individual T cells with their corresponding TCR-0 gene rearrangement and secreted products.

Public Health Relevance

This proof of concept study will provide a solid foundation for future applications in examining other Individual cell populations in the glands, especially B cells and natural killer cells in this disease. This study will reveal a better understanding of the biological and immunological interaction of each individual infiltrating cell. Results are expected to provide possible therapeutic approaches to the treatment of the disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Transition Award (R00)
Project #
5R00DE018958-05
Application #
8518291
Study Section
Special Emphasis Panel (NSS)
Program Officer
Burgoon, Penny W
Project Start
2011-09-01
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2013
Total Cost
$226,521
Indirect Cost
$71,899
Name
University of Florida
Department
Dentistry
Type
Schools of Dentistry
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Esfandiary, Lida; Gupta, Nirupama; Voigt, Alexandria et al. (2016) Single-cell antibody nanowells: a novel technology in detecting anti-SSA/Ro60- and anti-SSB/La autoantibody-producing cells in peripheral blood of rheumatic disease patients. Arthritis Res Ther 18:107
Lai, Zhennan; Yin, Hongen; Cabrera-Pérez, Javier et al. (2016) Aquaporin gene therapy corrects Sjögren's syndrome phenotype in mice. Proc Natl Acad Sci U S A 113:5694-9
Lavoie, Tegan N; Carcamo, Wendy C; Wanchoo, Arun et al. (2016) IL-22 regulation of functional gene expression in salivary gland cells. Genom Data 7:178-84
Voigt, Alexandria; Nguyen, Cuong Q (2015) Human T-Lymphotrophic Virus Type-I: A Unique Association with Myelopathy in Sjögren's Syndrome. Clin Microbiol 4:
Donate, Amy; Voigt, Alexandria; Nguyen, Cuong Q (2014) The value of animal models to study immunopathology of primary human Sjögren's syndrome symptoms. Expert Rev Clin Immunol 10:469-81
Voigt, Alexandria; Sukumaran, Sukesh; Nguyen, Cuong Q (2014) Beyond the Glands: An in-Depth Perspective of Neurological Manifestations in Sjögren's Syndrome. Rheumatology (Sunnyvale) 2014:
Nguyen, Cuong Q; Ogunniyi, Adebola O; Karabiyik, Afife et al. (2013) Single-cell analysis reveals isotype-specific autoreactive B cell repertoires in Sjögren's syndrome. PLoS One 8:e58127
Nguyen, Cuong Quoc; Peck, Ammon Broughton (2013) The Interferon-Signature of Sjögren's Syndrome: How Unique Biomarkers Can Identify Underlying Inflammatory and Immunopathological Mechanisms of Specific Diseases. Front Immunol 4:142
Karabiyik, A; Peck, A B; Nguyen, C Q (2013) The important role of T cells and receptor expression in Sjögren's syndrome. Scand J Immunol 78:157-66
Peck, A B; Nguyen, C Q (2012) Transcriptome analysis of the interferon-signature defining the autoimmune process of Sjögren's syndrome. Scand J Immunol 76:237-45

Showing the most recent 10 out of 20 publications