FoxO1 suppresses IL-10 producing B cell differentiation via negatively regulating Blimp-1 expression and contributes to allergic asthma progression

Song Rong Wang, Ren Dong Hu, Min Ma, Xing You, Haiyan Cui, Yi He, Damo Xu, Zhi Bin Zhao, Carlo F Selmi, M. Eric Gershwin, Liang Li, Zhe Xiong Lian

Research output: Contribution to journalArticlepeer-review

Abstract

IL-10-producing B cells (B10) are involved in the prevention of autoimmune and allergic responses but its mechanisms remain poorly understood. We took advantage of the ovalbumin-induced asthma mouse model to demonstrate that the activity of FoxO1 is upregulated in lung B cells and correlates inversely with B10 cells, while showing decreased activity in ex vivo and in vitro induced B10 cells. We further observed that FoxO1 deficiency leads to increased frequency of B10 cells. These observations have in vivo clinical evidence, as B cell specific FoxO1 deficiency leads to reduced lung eosinophils and asthma remission in mice, and there are reduced regulatory B cells and increased FoxO1 activity in B cells of asthma patients. Single cell RNA-sequencing data demonstrated a negative correlation between the expression of Foxo1 and Il10 in B cells from the mouse spleen and lung and the human lung. For a biological mechanism, FoxO1 inhibits the expression of Prdm1, which encodes Blimp-1, a transcription factor of B10 cells. Our experimental evidence in both murine and human asthma demonstrates that FoxO1 is a negative regulator of B10 cell differentiation via negatively regulating Prdm1 and its expression in B cells contributes to allergic asthma disease. [Figure not available: see fulltext.].

Original languageEnglish (US)
JournalMucosal Immunology
DOIs
StateAccepted/In press - 2022

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'FoxO1 suppresses IL-10 producing B cell differentiation via negatively regulating Blimp-1 expression and contributes to allergic asthma progression'. Together they form a unique fingerprint.

Cite this