Skip to main content
. Author manuscript; available in PMC: 2017 Apr 1.
Published in final edited form as: J Allergy Clin Immunol. 2016 Apr;137(4):984–997. doi: 10.1016/j.jaci.2016.02.004

Figure 1. A model of how the gut promotes tolerance or sensitization.

Figure 1

Protein antigens (Ags) pass through the epithelial barrier via multiple mechanisms including capture by transluminal processes of CX3CR1+ cells. CD103+ dendritic cells (DCs) then capture Ag, migrate to the mesenteric lymph nodes (MLNs), and present Ag to naïve T cells. In tolerance (A), this interaction promotes the generation of Tregs via 1) production of retinoic acid (RA) by MLN, 2) DC expression of IDO, 3) DC secretion of TGFβ, and 4) DC upregulation of αvβ8 to activate latent TGFβ. Gut homing receptors, CCR9 and α4β7, are upregulated on newly formed Tregs. RA and DC interactions also stimulate differentiation of IgA producing B cells. In sensitization (B), epithelial disruption allows increased antigen penetration, and promotes production/release of epithelial cytokines (IL-33, TSLP and IL-25) that upregulate OX40 ligand (OX40L) on DCs. DCs then promote differentiation of naïve T cells to Th2 cells producing cytokines that recruit eosinophils (IL-5) and promote IgE class switching in B cells (IL-4 and IL-13). IgE may facilitate Ag uptake through CD23.

HHS Vulnerability Disclosure