PI3K-Akt pathway modulates IL-10 producing regulatory B cell

Abstract

Introduction: IL-10 producing regulatory B (Breg) cells negatively regulate autoimmune disease and inflammation, such as contact hypersensitivity (CHS). CD19 expression is critical for Breg cells development, since CD19 loss results in decreased number of Breg cell and increased reactivity of CHS, which is ameliorated by the adoptive transfer of Breg cells from wild-type mice. However, molecular mechanism of Breg cell development remains poorly understood. CD19 downstream signal is depend on the activation of phosphoinositide 3-kinases (PI3 K)-Akt pathways, while phosphatase and tensin homologue (PTEN) attenuates PI3K-Akt pathways. In this study, we investigated the role of PI3K-Akt pathway in the development of Breg cells.Method: The effect of PI3K-Akt pathway inhibitors on Breg cell development was examined in vitro. B cell-specific PTEN deficient mice, which exhibit aberrant activation of PI3K-Akt pathway in B cell, were generated using Cre-loxp system. CHS severity in B cell-specific PTEN deficient mice was investigated. Result: The current studies demonstrate that PI3K-Akt pathway inhibitors reduced Breg cells in vitro in dose-dependent manner. However, PTEN inhibitor had no effect on Breg cells. Breg cell number and frequency were significantly increased in various organs of B cell-specific PTEN deficient mice when compared with wild-type mice. Furthermore, CHS response was significantly diminished in B cell-specific PTEN deficient mice when compared with wild-type mice. Thus, PI3K-Akt pathway positively regulates Breg cell development, while PTEN negatively regulates it. Conclusion: PI3K-Akt pathway in B cell is critical for Breg cell development and could be a potent therapeutical target. JSID AbstractsJournal of Dermatological ScienceVol. 69Issue 2Preview Full-Text PDF