Autophagy occurs in lymphocytes infiltrating Sjögren’s syndrome minor salivary glands and correlates with histological severity of salivary gland lesions

Arthritis Research & Therapy

Francesco Ciccia¹  Bruna Cerbelli²  Carla Giordano²  Francesca Arienzo³  Raffaella Izzo³  Roberta Priori³  Marta Vomero³  Linda Mastromanno³  Guido Valesini³  Antonina Minniti³  Cristiano Alessandri³  Serena Colafrancesco³  Tania Colasanti³  Fabrizio Conti³  Cristiana Barbati³  Elena Pipi⁴  Valentina Iannizzotto⁴  Saba Nayar⁴  Francesca Barone⁵ 

[1] Dipartimento di Medicina di Precisione, Rheumatology Unit, University of Campania “L. Vanvitelli”, Naples, Italy;Dipartimento di Radiologia, Oncologia e Scienze Patologiche, Sapienza University of Rome, Rome, Italy;Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Sapienza University of Rome, Rome, Italy;Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK;Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK;National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, UK and Sandwell and West Birmingham Trust, Birmingham, UK;

关键词: Autophagy;    Lymphocytes;    Sjögren’s syndrome;    Minor salivary gland;    LC3B;    Atg5;   

DOI  :  10.1186/s13075-020-02317-6

来源: Springer

【 摘 要 】

BackgroundsThe organization of minor salivary glands (MSG) infiltrates, in patients with Sjögren’s syndrome (SS), associates with disease severity and progression. Aberrant regulation of lymphocyte autophagy is involved in autoimmunity, and in previous work, we provided the first evidence of upregulated autophagy in CD4+ T cells infiltrating SS MSG. The aim of this study was to further explore autophagy in SS infiltrating and circulating lymphocytes and to investigate its role in disease histopathological progression.MethodsAfter collection of 20 SS MSG, the presence of lymphocyte aggregates (foci) and the formation of germinal center (GC)-like structures were observed by H&E and confirmed by immunohistochemistry. The expression of autophagy-related genes, Atg5 and MAP1LC3A, was detected by RT-PCR on microdissected salivary gland tissue and control tonsils. In MSG and tonsils, autophagic lymphocytes were identified by the detection of the autophagosome protein LC3B visualized as LC3 puncta staining by immunofluorescence. Peripheral blood autophagy was assessed by flow cytometry in SS and healthy controls (HC).ResultsReal-time PCR demonstrated higher expression in the autophagy genes Atg5 and MAP1LC3A in MSG GCs as compared to both small foci (p = 0.0075, p = 0.0002) and GCs from tonsils (p = 0.0001, p = 0.0037). In MSG, LC3 puncta staining was detectable on both CD3+ and CD20+ lymphocytes; in tonsils, LC3 puncta was almost undetectable on all lymphocytes. Compared to HC (n = 20), flow cytometry did not reveal any increase of autophagy in SS circulating lymphocytes (n = 30).ConclusionsIn SS MSG, lymphocytes’ autophagy is a feature of infiltrating T and B cells and is associated with histological severity. Interestingly, in MSG aberrant regulation of autophagy is detectable in GC-like structures possibly indicating its involvement in the development and persistence of the autoimmune process within the lesions.

【 授权许可】

CC BY