Roles of Regulatory T and B Cells in IgG4-Related Disease

Immunoglobulin G4 (IgG4) -related disease (RD) is a newly recognized systemic disease. Although there are several forms of IgG4-RD reported under various names, depending on the target organ and characteristics, patients with IgG4-RD manifest several immunologic and histologic abnormalities including increased levels of serum IgG4 and storiform fibrosis with infiltration of lymphocytes and IgG4-positive plasmacytes in the involved organs. However, the pathophysiology remains unclear. Regulatory immune cells play an important role in several immune-related diseases. In particular, abnormalities in regulatory T cell (Treg) and regulatory B cell (Breg) numbers and function are implicated in several immune-related (include autoimmune) conditions, and their roles in IgG4-RD have recently begun to be investigated. We provide an overview of the research conducted to date on Tregs and Bregs in IgG4-RD. We highlight the basic functions of these cells, their changes in patients with various forms of IgG4-RD, and insight gained from animal models of the disease. Based on the evidence accumulated thus far, we proposed a hypothesis for the pathophysiological mechanism of IgG4-RD with respect to the roles regulatory immune cells, and highlight the questions and venues of research deserving of further attenuation, Over all, we demonstrate that Tregs and Bregs have a clear impact on IgG4-RD, and further exploration of this field is expected to lead to a better mechanistic understanding of the disease, hopefully resulting in the in the discovery of new therapeutic targets.