Short-Chain Fatty Acid Sodium Butyrate Suppresses Protective Humoral Immunity by Inhibiting Follicular T Helper Cell...

Area of Science:

• Immunology
• Microbiome Research
• Metabolomics

Background:

• The gut microbiome influences host immunity and vaccine responses.
• Humoral immunity relies on germinal centers (GCs) and follicular T helper (Tfh) cells.
• Short-chain fatty acids (SCFAs) are key gut microbial metabolites.

Purpose of the Study:

• To investigate the role of SCFAs, specifically sodium butyrate, in regulating Tfh cell differentiation and humoral immunity.
• To elucidate the mechanisms by which sodium butyrate affects Tfh cell function.

Main Methods:

• Ex vivo assays to assess sodium butyrate's direct effects on Tfh cells.
• Antigen-specific and influenza virus infection models in mice.
• Histone deacetylase (HDAC) inhibition assays.

Main Results:

• Sodium butyrate, but not acetate or propionate, directly suppressed Tfh cell differentiation and function.
• In vivo, sodium butyrate impaired Tfh cell differentiation, reducing GC B cell responses and humoral immunity during influenza infection.
• Sodium butyrate treatment led to increased susceptibility to viral infection in mice.
• The suppressive effects were mediated by histone deacetylase (HDAC) inhibition.

Conclusions:

• Sodium butyrate acts as a negative regulator of humoral immunity by directly inhibiting Tfh cell differentiation and GC responses.
• This study establishes a mechanistic link between gut microbiome metabolites and the regulation of adaptive immunity.
• Findings have implications for understanding vaccine efficacy and developing microbiome-based therapeutics.