NKp30 Receptor Upregulation in Salivary Glands of Sjögren's Syndrome Characterizes Ectopic Lymphoid Structures and Is Restricted by Rituximab Treatment.

Pontarini, Elena, Sciacca, Elisabetta, Grigoriadou, Sofia, Rivellese, Felice, Lucchesi, Davide, Fossati-Jimack, Liliane, Coleby, Rachel, Chowdhury, Farzana, Calcaterra, Francesca, Tappuni, Anwar, Lewis, Myles J, Fabris, Martina, Quartuccio, Luca, Bella, Silvia Della, Bowman, Simon J, Pitzalis, Costantino, Mavilio, Domenico, De Vita, Salvatore and Bombardieri, Michele (2021) NKp30 Receptor Upregulation in Salivary Glands of Sjögren's Syndrome Characterizes Ectopic Lymphoid Structures and Is Restricted by Rituximab Treatment. Frontiers in immunology, 12. p. 706737. ISSN 1664-3224. This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs

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Abstract

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease resulting from the inflammatory infiltration of exocrine glands, mainly salivary and lacrimal glands, leading to secretory dysfunction and serious complications including debilitating fatigue, systemic autoimmunity, and lymphoma. Like other autoimmune disorders, a strong interferon (IFN) signature is present among subsets of pSS patients, suggesting the involvement of innate immunity in pSS pathogenesis. /NKp30 is a natural killer (NK) cell-specific activating receptor regulating the cross talk between NK and dendritic cells including type II IFN secretion upon NK-cell activation. A genetic association between single-nucleotide polymorphisms (SNPs) in the /NKp30 promoter gene and a higher susceptibility for pSS has been previously described, with pSS patients most frequently carrying the major allele variant associated with a higher NKp30 transcript and IFN-γ release as a consequence of the receptor engagement. In the present study, we combined RNA-sequencing and histology from pSS salivary gland biopsies to better characterize NKp30 () and its ligand B7/H6 () in pSS salivary gland tissues. Levels of /NKp30 were significantly increased both in salivary glands and in circulating NK cells of pSS patients compared with sicca controls, especially in salivary glands with organized ectopic lymphoid structures. In line with this observation, a strong correlation between /NKp30 levels and salivary gland infiltrating immune cells (CD3, CD20) was found. Furthermore, /NKp30 levels also correlated with higher IFN-γ, Perforin, and Granzyme-B expression in pSS SGs with organized ectopic lymphoid structures, suggesting an activation state of NK cells infiltrating SG tissue. Of note, NKp30+ NK cells accumulated at the border of the inflammatory , while the NKp30 ligand, B7/H6, is shown to be expressed mainly by ductal epithelial cells in pSS salivary glands. Finally, immunomodulatory treatment, such as the B-cell depleting agent rituximab, known to reduce the infiltration of immune cells in pSS SGs, prevented the upregulation of /NKp30 within the glands.

Item Type: Article
Additional Information: This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs
Subjects: QW Microbiology. Immunology
WD Diseases and disorders of systemic, metabolic or environmental origin > WD811 Rheumatology
WU Dentistry. Oral surgery
Divisions: Ambulatory Care > Rheumatology
Related URLs:
Depositing User: Jamie Edgar
Date Deposited: 12 Oct 2021 13:37
Last Modified: 12 Oct 2021 13:37
URI: http://www.repository.uhblibrary.co.uk/id/eprint/4703

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