Highlights d Stool butyrate levels are reduced in patients with RA compared to healthy controls d Supplementation with butyrate suppresses arthritis severity in a mouse model d Suppression of arthritis by butyrate supplementation depends upon AhR + Bregs d Butyrate increases serotonin-derived 5-HIAA, which directly activates AhR + Bregs

Regulatory B cells (Bregs) is a term that encompasses all B cells that act to suppress immune responses. Bregs contribute to the maintenance of tolerance, limiting ongoing immune responses and reestablishing immune homeostasis. The important role of Bregs in restraining the pathology associated with exacerbated inflammatory responses in autoimmunity and graft rejection has been consistently demonstrated, while more recent studies have suggested a role for this population in other immune-related conditions, such as infections, allergy, cancer, and chronic metabolic diseases. Initial studies identified IL-10 as the hallmark of Breg function; nevertheless, the past decade has seen the discovery of other molecules utilized by human and murine B cells to regulate immune responses. This new arsenal includes other anti-inflammatory cytokines such IL-35 and TGF-β, as well as cell surface proteins like CD1d and PD-L1. In this review, we examine the main suppressive mechanisms employed by these novel Breg populations. We also discuss recent evidence that helps to unravel previously unknown aspects of the phenotype, development, activation, and function of IL-10-producing Bregs, incorporating an overview on those questions that remain obscure.

Although no changes were detected in the frequency of Th1 or Th17 cells, the percentages of peripheral Tregs increased after therapy. In addition, the infrequent Th17/Th1 subpopulation showed a significant increment in tocilizumab-treated patients. In conclusion, tocilizumab was able to skew the balance between Th17 cells and Tregs towards a more protective status, which may contribute to the clinical improvement observed in RA patients.