ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2292

Fibroblasts with High Expression of CD74 Promote Lymphocytes Infiltration in Salivary Gland in Sjӧgren’s Disease

Xinwei zhang1, Yixuan Li1, Hongyan Qian1, Chaoqiong Deng1, Shiju Chen1, Guixiu Shi2 and Yuan Liu1, 1xiamen university, xiamen, China (People's Republic), 2xiamen university, xiamen

Meeting: ACR Convergence 2024

Keywords: ,

Session Information

Date: Monday, November 18, 2024

Title: Sjögren's Syndrome – Basic & Clinical Science Poster II

Session Type: Poster Session C

Session Time: 10:30AM-12:30PM

Background/Purpose: Sjӧgren’s disease (SjD) is characterized by persistent focal infiltration of B- and T lymphocytes in the exocrine gland, mainly salivary gland. Though it is well recognized that the infiltrating lymphocytes is the main cause that leads to gland dysfunction, the mechanisms in how lymphocytes are recruited and persistently activated in salivary gland have not been fully investigated.

Methods: We performed single-cell RNA-sequencing (scRNA-seq) combined with spatial transcriptomics on minor salivary glands (MSGs) from patients with SjD and controls. The crosstalk between stromal cells and immune cells was analyzed. Potential pathogenic cell subsets that may be involved in promoting lymphocytes infiltration were further investigated by ex vivo culture assays and SjD animal model.

Results: The scRNA-seq demonstrated that several cytokines that are important in recruiting and activating lymphocytes such as CXCL12 and BAFF were prominently enriched in fibroblasts, and spatial transcriptomics analysis revealed that fibroblasts were closely associated with lymphocytes. CD74 expression significantly increased in salivary fibroblasts in patients with SjD, and fibroblasts subcluster with high expression of CD74 expanded in patients with SjD, which was enriched in pathways associated with lymphocytes activation and cytokine production. In the in vitro co-culture assay of fibroblasts with B cells, fibroblasts with high expression of CD74 can promote B cell proliferation and survival, while CD74 knockout in fibroblasts diminished this effect. CD74 knockout in mice and anti-CD74 antibody can decrease lymphocytes infiltration in exocrine gland and alleviate the gland dysfunction.

Conclusion: Fibroblasts with high expression of CD74 was pathogenic fibroblasts subsets in SjD, which may be important in promoting lymphocytes infiltration in salivary gland. Targeting CD74 may provided new effective treatment strategy for SjD.

Supporting image 1

Cytokines associated with lymphocytes recruiting and activation were enriched in salivary fibroblasts.

Supporting image 2

Expression of CD74 was associated with the proximity of fibroblasts and immune cells in salivary gland.

Supporting image 3

Anti-CD74 antibody can decrease lymphocytes infiltration in exocrine gland and alleviate the gland dysfunction in SjD mouse model.

Disclosures: X. zhang: None; Y. Li: None; H. Qian: None; C. Deng: None; S. Chen: None; G. Shi: None; Y. Liu: None.

To cite this abstract in AMA style:

zhang X, Li Y, Qian H, Deng C, Chen S, Shi G, Liu Y. Fibroblasts with High Expression of CD74 Promote Lymphocytes Infiltration in Salivary Gland in Sjӧgren’s Disease [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/fibroblasts-with-high-expression-of-cd74-promote-lymphocytes-infiltration-in-salivary-gland-in-sj%d3%a7grens-disease/. Accessed .

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