Journal
CELL DEATH & DISEASE
Volume 12, Issue 6, Pages -Publisher
SPRINGERNATURE
DOI: 10.1038/s41419-021-03880-9
Keywords
-
Categories
Funding
- Guangzhou Basic and Applied Basic Research Foundation [202002030127]
- Guangdong Basic and Applied Basic Research Foundation [2021A1515012324]
- Program for Guangdong Introducing Innovative and Entrepreneurial Teams [2016ZT06S252]
- Fundamental Research Funds for the Central Universities [20ykzd08]
- Natural Science Foundation of Guangdong Province [2018A030313563]
- Guangdong Financial Fund for High-Caliber Hospital Construction
- National Natural Science Foundation of China [31800006]
Ask authors/readers for more resources
B10 cells, a subtype of regulatory B cells crucial for immune homeostasis, can be promoted by short-chain fatty acids (SCFAs) through activating the p38 MAPK pathway. This upregulation of B10 cells by SCFAs alleviates clinical symptoms of colitis and arthritis. The mechanism involves histone deacetylase (HDAC) inhibition and independent of the G-protein-coupled receptor pathway.
B10 cells are regulatory B cells capable of producing IL-10 for maintaining immune homeostasis. Dysregulation of B10 cells occurs in autoimmune and inflammatory diseases. Modulation or adoptive transfer of B10 cells is a promising therapeutic strategy. The short-chain fatty acids (SCFAs), the metabolites of microbiota, play a critical role in maintaining immune homeostasis and are the potential drugs for the modulation of B10 cells. It is not clear whether and how SCFAs upregulate the frequency of B10 cells. Here, we found that SCFAs could promote murine and human B10 cell generation in vitro. Upregulation of B10 cells by butyrate or pentanoate was also observed in either healthy mice, mice with dextran sodium sulfate (DSS)-induced colitis, or mice with collagen-induced arthritis. Moreover, SCFA treatment could ameliorate clinical scores of colitis and arthritis. Adoptive transfer of B cells pretreated with butyrate showed more alleviation of DSS-induced colitis than those without butyrate. A further study demonstrates that SCFAs upregulate B10 cells in a manner dependent on their histone deacetylase (HDAC) inhibitory activity and independent of the G-protein-coupled receptor pathway. Transcriptomic analysis indicated that the MAPK signaling pathway was enriched in B10 cells treated with butyrate. A study with inhibitors of ERK, JNK, and p38 MAPK demonstrated that activating p38 MAPK by butyrate is critical for the upregulation of B10 cells. Moreover, HDAC inhibitor has similar effects on B10 cells. Our study sheds light on the mechanism underlying B10 cell differentiation and function and provides a potential therapeutic strategy with SCFAs and HDAC inhibitors for inflammation and autoimmune diseases.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available