Primary Sjögren's syndrome (pSS) is a systemic chronic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands causing tissue destruction. The major tissues damaged are the salivary and lacrimal glands, resulting in decreased secretion of saliva and tears [1]. The pathophysiology of pSS is more complicated and still not well understood. Current research suggests that autoimmune dysregulation, including activation of T helper and B cells, is thought to be a significant factor underlying the pathological process [2], [3]. Although significant progress has been made in the clinical treatment of pSS with glucocorticoids in combination with synthetic anti-rheumatic drugs, the exocrine function of patients has not improved. Hence, there is an urgent requirement to develop novel immunosuppressive therapies for the treatment of pSS.

Recently, Mesenchymal stem cells (MSC) transplantation has been proven as the most promising cell-based treatment option for a variety of autoimmune diseases [4], [5], [6] including pSS. However, autologous MSC transplantation is not effective in treating patients and allogeneic MSC transplantation is required [7]. MSC homing refers to the targeted migration of MSC toward the site of the lesion [8], [9], [10], which is the basis for MSC to become a cell-based therapy. We previously found that pSS-BMMSC showed significant defectiveness of the immunoregulatory function [7], but whether the migration and proliferation of pSS-BMMSC are impaired needs to be clarified.

Cofilin 1 (CFL1), an actin-depolymerizing factor (ADF)/cofilin family isoform, is associated with a variety of diseases and environmental homeostasis in vivo [11], [12]. CFL1 has been implicated in the regulation of cell growth and migration in recent studies. Hypoxia-induced CFL1 drives hepatocellular carcinoma cell migration by activating the AKT signal pathway via inhibition of ubiquitin-mediated protein degradation to stabilize PLD1 expression [13]. CFL1 promotes the migration of colorectal cancer cells by activating the RhoA-LIMK2-cofilin-1 signaling pathway and enhancing actin cytoskeleton reorganization [14]. However, the relationship between CFL1 and the migratory and proliferative abilities of MSC remains uncertain.

The abnormal function of autologous BM-MSC may be essential in the pathogenesis of pSS. In this research, we demonstrated the decreased migratory and proliferative ability of pSS-BMMSC and the reduced expression of CFL1. Our data showed that overexpression of CFL1 could improve the migration and proliferation capacity of pSS-BMMSC. What’s more, we found that CFL1 modifications in BM-MSC can improve their migration towards injured SMGs of NOD mice by regulating the CCL5/CCR1 axis. To our knowledge, this finding was the first attempt to explore the mystery of MSC treatment of pSS based on the CFL1/CCL5/CCR1 mechanism.