CD27+TIM-1+ memory B cells promoted the development of Foxp3+ Tregs and were associated with better survival in acute respiratory distress syndrome

Abstract

Acute respiratory distress syndrome (ARDS) is a rapid onset life-threatening condition involving uncontrolled propagation of inflammatory responses. Here, we observed that ARDS patients that survived presented significantly higher frequencies of TIM-1⁺ B cells, especially the CD27⁺TIM-1⁺ B cells, than the ARDS patients who succumbed to the condition. We then found that using BCR/CD40 antigen-dependent stimulation or Staphylococcus aureus Cowan (SAC) antigen-independent stimulation, TIM-1⁺ B cells presented significantly higher IL-10 secretion and/or TGF-β1 secretion, with SAC stimulation being more effective. CD4⁺ T cells that incubated with TIM-1⁺ B cells presented significantly elevated IL-10 secretion, TGF-β1 secretion, and Foxp3 expression, than CD4⁺ T cells that incubated with TIM-1^- B cells, suggesting TIM-1⁺ B cells promoted the in vitro development of Foxp3⁺ Treg cells. Interestingly, this TIM-1⁺ B cell-mediated promotion of Foxp3 expression was mostly dependent on TGF-β1 but not IL-10, since neutralization of TGF-β1, but not IL-10, resulted in the suppression of Foxp3 expression. We further showed that in TIM-1⁺ B cells, the CD27⁺ classical memory B cell subset demonstrated more regulatory potency than the CD27^- subset. Together, our results suggested that the TIM-1⁺ B cells, especially those that expressed CD27, could promote Foxp3 expression. Their clinical efficacy in treating ARDS should be examined in in vivo experiments.

Keywords: ALI; Breg; IL-10; TIM-1+ B cell.