Abstract BACKGROUND FoxP3+ regulatory T cells (Tregs) are crucial to self- and antigen-specific tolerance. IL-33 drives expansion of Tregs expressing the IL-33 receptor, ST2, and secreting high levels of IL-10. Regulatory B cells (Bregs) are recently identified negative regulators of the immune system and depend on IL-10 to suppress effector T cell responses. In new data, we find that IL-33 also expands Bregs, however, the relationship between ST2+ Treg and Bregs cells remains unknown. Herein we elucidated if a directional relationship exists between IL-33-expanded Bregs and Tregs. METHODS B6 eGFP-FoxP3-Diptheria Toxin (DT) receptor mice were used to establish whether IL-33-expanded Treg were needed for IL-33-aided increases of TIM-1+ IL-10+ Bregs. B6 Foxp3-Cre X IL-10fl/fl mice were used to determine the need for IL-10 expression by Tregs for IL-33-mediated expansion of Bregs. RESULTS Assessment of splenocytes for Tregs and Bregs by flow cytometry showed that IL-33 administration led to a 3–5-fold increase in ST2+ Tregs. IL-33 also led to a 3-fold increase in the frequency of IL-10+ Breg, most of which expressed ST2. A lack of Tregs hindered the ability of IL-33 to increase Bregs. While Treg expression IL-10 was not required for ST2+ Treg expansion by IL-33, IL-10 expression by Tregs is crucial for Breg expansion by IL-33. CONCLUSIONS We have uncovered a relationship between Tregs and Bregs in response to IL-33. Specifically, while we show that Bregs express ST2, our data suggest that IL-33 expansion of Bregs is indirectly mediated by Treg IL-10 production.