Abstract
Background: B cells play an important role in the development and maintenance of rheumatoid arthritis (RA). Although IL-10–producing B cells represent a major subset of regulatory B cells (Bregs) able to suppress autoimmune and inflammatory responses, recent reports showed that B cell-mediated immune suppression may also occur independent of IL-10. For instance, B cells can modulate T cell immune responses through the expression of regulatory molecules such as PD-L1. So far, PD-L1-expressing B cells have not been analyzed in RA patients.Objective: To analyze the frequency of PD-L1-expressing B cells in the peripheral blood of RA patients compared to healthy controls (HC) matched for sex and age, their function on T cell response and their changes in response to therapy.Methods: Fresh peripheral blood B cells from RA patients and HC were characterized by flow cytometry and their functionality assessed in a co-culture system with autologous T cells.Results: The frequencies of CD19+PD-L1+ B cells, CD24hiCD38−PD-L1+ and CD24hiCD38hiPD-L1+ B cells were significantly lower in untreated RA patients than in HC. In a follow-up study, the frequencies of PD-L1+ B cells (CD19+PD-L1+ B cells, CD24hiCD38−PD-L1+ and CD24hiCD38hiPD-L1+ B cells) increased significantly after treatment in good responder patients, although the frequency of total CD24hiCD38hi B cells decreased. CD19+ B cells from untreated RA patients and HC upregulated PD-L1 expression similarly upon stimulation with CpG plus IL-2 and were able to suppress, in vitro, CD8+ T cell proliferation and cytokine production in a PD-L1-dependent manner.Conclusions: Our results show that PD-L1+ B cells exhibiting T cell suppressive capacity are significantly decreased in untreated RA patients but increase in response to successful treatment. PD-L1 expression on B cells from RA patients can be modulated in vitro and PD-L1+ B cells could thus provide new perspectives for future treatment strategies.
Highlights
Rheumatoid arthritis (RA) is a chronic, potentially debilitating inflammatory disease, characterized by destructive synovitis that, if left untreated, results in significant pain, swelling, stiffness, loss of function in the joints, deformity and disability [1]
Peripheral blood samples were collected from 25 healthy controls (HC), 26 untreated RA patients, 20 RA patients treated with methotrexate (MTX), 20 treated with TNF inhibitors and 14 treated with JAK inhibitor, Tofacitinib
Peripheral blood samples were obtained from healthy controls (HC, n = 25), untreated RA patients and RA patients treated with methotrexate (MTX, n = 20), TNF inhibitors, and the JAK inhibitor Tofacitinib (TOFA, n = 14)
Summary
Rheumatoid arthritis (RA) is a chronic, potentially debilitating inflammatory disease, characterized by destructive synovitis that, if left untreated, results in significant pain, swelling, stiffness, loss of function in the joints, deformity and disability [1]. Tissue inflammation and damage is mediated through several cell types, including T cells, B cells, monocytes, macrophages, fibroblasts, and osteoclasts [2, 3]. The PD-1/PD-L1 pathway appears as a potential immune checkpoint to control the inflammation in RA patients. B cells play an important role in the development and maintenance of rheumatoid arthritis (RA). IL-10–producing B cells represent a major subset of regulatory B cells (Bregs) able to suppress autoimmune and inflammatory responses, recent reports showed that B cell-mediated immune suppression may occur independent of IL-10. PD-L1-expressing B cells have not been analyzed in RA patients
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