Figure 3.

Widespread effects of butyrate on immune cells in allergic asthma. Allergic asthma is a complex inflammatory disease with several immune cells involved in the pathogenesis. Exposure to an allergen induces eosinophilia, airway hyperreactivity, and goblet cell hyperplasia. These effects are collectively driven by dendritic cells (DCs), Th2 cells, Th9 cells, ILC2s, B cells, mast cells, and eosinophils. Butyrate ameliorates allergic asthma by modulating various steps in pathways of different immune cell compartments. Butyrate suppresses both DC activation and migration to local lymph nodes where activated DCs function to stimulate immature/naive CD4+ T cells to polarize to the Th2 lineage. In the B cell compartment, butyrate suppresses both B cell isotype class switching and plasma cell differentiation leading to decreased levels of circulating IgE. Subsequent binding of allergens and cross-linking of surface bound IgE to Fc receptors expressed on mast cells induces degranulation; however, butyrate inhibits IgE-mediated mast cell degranulation. In the Th9 cell lineage, butyrate functions to divert the fate of naïve CD4+ T cells from Th9 to FoxP3+ regulatory-T cells (T regs) effectively promoting a regulatory phenotype. In ILC2s, butyrate suppresses the secretion of IL-5 and IL-13 cytokines that have downstream effects on eosinophils. Butyrate inhibits both the adhesion of eosinophils to the blood vessel endothelium, chemotaxis in response to CCL24, and directly promotes eosinophil apoptosis. Created with https://biorender.com/.