The immunopathogenesis of Sjögren’s and the active role of the glandular epithelium is not entirely understood thus limiting therapeutic approaches. We found for the first time, in human and mouse salivary glands, that ductal epithelial cells overexpress the prostanoid receptor CRTH2 during Sjögren’s autoimmunity. Importantly, CRTH2 blockade is a promising therapeutic strategy in asthma. Also, we found that innate lymphoid cells (ILCs), a subset of epithelium-associated leukocytes, infiltrate salivary glands and show pro-inflammatory properties in Sjögren’s and its murine model (autoimmune regulator knock-out). We hypothesize that ductal epithelial cell activation via CRTH2 ligation leads to ILC activation and recruitment, thus perpetuating the inflammatory response. This translational project aims to investigate the pathogenic features of salivary epithelial cells and ILCs on Sjögren’s in humans and murine models and might potentially lead to new therapeutic/diagnostic approaches. SSF Research Grant Reviewers concluded that “understanding the epithelial cell/immune cell interface is highly important in further understanding Sjögren’s pathogenesis. [There is a] high probability that significant findings will come from this project.” Danielle Marie Robertson, BS, OD, PhD Associate Professor, University of Texas Southwestern Medical Center, Department of Ophthalmology, Dallas, Texas Research Project Comparative Structural and Molecular Analysis of Tear and Salivary Derived Exosomes in Sjögren’s Syndrome Abstract The major problem facing Sjögren’s patients and clinicians today remains the absence of effective biomarkers to allow for early detection and treatment of the disease. Based upon available data, we propose to test a hypothesis that saliva and tear derived from exosomes will contain biomarkers unique to patients with primary Sjögren’s. We will test this hypothesis by characterizing the ultrastructural biology and molecular signature of saliva and tear derived exosomes from women with primary SS compared to age-matched healthy controls using cryo-electron microscopy and next generation RNA-sequencing. The identification and characterization of the exosomal structure and molecular profile is the first step in the identification of novel, early biomarkers for Sjögren’s. Upon review, an SSF Research Grant Reviewer felt that “this study has the potential of elucidating new biomarkers for Sjögren’s,” which could prove a very important advancement to the field. Additionally, this project involves a “newly formed Center of Excellence for Sjögren’s Clinical Care and Research that is multi-disciplinary andThe major problem facing Sjögren’s patients and clinicians today remains the absence of effective biomarkers to allow for early detection and treatment of the disease. Based upon available data, we propose to test a hypothesis that saliva and tear derived from exosomes will contain biomarkers unique to patients with primary Sjögren’s. We will test this hypothesis by characterizing the ultrastructural biology and molecular signature of saliva and tear derived exosomes from women with primary SS compared to age-matched healthy controls using cryo-electron microscopy and next generation RNA-sequencing. The identification and characterization of the exosomal structure and molecular profile is the first step in the identification of novel, early biomarkers for Sjögren’s. Upon review, an SSF Research Grant Reviewer felt that “this study has the potential of elucidating new biomarkers for Sjögren’s,” which could prove a very important advancement to the field. Additionally, this project involves a “newly formed Center of Excellence for Sjögren’s Clinical Care and Research that is multi-disciplinary and involves an excellent team and infrastructure.” Daniela Cihakova, MD, PhD Danielle Marie Robertson, BS, OD, PhD Continued on page 12 t Sjögren’s Quarterly 9

Members Esen Akpek, MD Herbert S. Baraf, MD, MACR Richard Brasington, MD, FACR Michael Brennan, DDS, MHS Steven E. Carsons, MD* Troy Daniels, DDS, MS* Denise L. Faustman, MD, PhD H. Kenneth Fisher, MD, FACP, FCCP Gary Foulks, MD, FACS Theresa Lawrence Ford, MD S. Lance Forstot, MD Philip C. Fox, DDS* Robert I. Fox, MD, PhD, FACP* Tara Mardigan, MS, MPH, RD Austin Mircheff, PhD John Daniel Nelson, MD, FACS Kelly Nichols, OD Athena Papas, DMD, PhD Ann Parke, MD Andres Pinto, DMD Nelson Rhodus, DMD, MPH Vidya Sankar, DMD, MHS Daniel Small, MD, FACP Neil Stahl, MD Frederick B. Vivino, MD, FACR Jeffrey Wilson, MD, FACR

Members Esen Akpek, MD Herbert S. Baraf, MD, MACR Richard Brasington, MD, FACR Michael Brennan, DDS, MHS Steven E. Carsons, MD* Troy Daniels, DDS, MS* Denise L. Faustman, MD, PhD H. Kenneth Fisher, MD, FACP, FCCP Gary Foulks, MD, FACS Theresa Lawrence Ford, MD S. Lance Forstot, MD Philip C. Fox, DDS* Robert I. Fox, MD, PhD, FACP* Tara Mardigan, MS, MPH, RD Austin Mircheff, PhD John Daniel Nelson, MD, FACS Kelly Nichols, OD Athena Papas, DMD, PhD Ann Parke, MD Andres Pinto, DMD Nelson Rhodus, DMD, MPH Vidya Sankar, DMD, MHS Daniel Small, MD, FACP Neil Stahl, MD Frederick B. Vivino, MD, FACR Jeffrey Wilson, MD, FACR

Members Richard Brasington, MD, FACR Michael Brennan, DDS, MHS Steven E. Carsons, MD* Troy Daniels, DDS, MS* H. Kenneth Fisher, MD, FACP, FCCP Gary Foulks, MD, FACS Theresa Lawrence Ford, MD Philip C. Fox, DDS* Tara Mardigan, MS, MPH, RD Austin Mircheff, PhD John Daniel Nelson, MD, FACS Kelly Nichols, OD Athena Papas, DMD, PhD Ann Parke, MD Andres Pinto, DMD Nelson Rhodus, DMD, MPH Daniel Small, MD, FACP Neil Stahl, MD Pamela Stratton, MD Frederick B. Vivino, MD, FACR

Members Richard Brasington, MD, FACR Steven E. Carsons, MD* Troy Daniels, DDS, MS* H. Kenneth Fisher, MD, FACP, FCCP Gary Foulks, MD, FACS Philip C. Fox, DDS* Tara Mardigan, MS, MPH, RD Austin Mircheff, PhD John Daniel Nelson, MD, FACS Kelly Nichols, OD Athena Papas, DMD, PhD Ann Parke, MD Andres Pinto, DMD Nelson Rhodus, DMD, MPH Daniel Small, MD, FACP Neil Stahl, MD Pamela Stratton, MD Frederick B. Vivino, MD, FACR