In the normal steady state, RA is involved in the secretion of transforming growth factor β (TGF-β) from antigen-presenting cells (APCs) and promotion of a CD4⁺ Treg phenotype as well as an overall reduced expression of proinflammatory cytokines. In the setting of GI-aGVHD, infiltration of triple-positive CD8⁺ T-effector (Teff) cells enriched for Tbet (Th1/Tc1 lineage), RARα, and IL-23R occurs in the intestinal subcrypt zone adjacent to intestinal epithelial stem cells. CD4⁺ Tregs are also expanded in the subcrypt zone in the setting of GI-aGVHD but to a much lesser extent. Both lineages likely derive from the peripheral blood in response to RA, where (modulated by IL-23/LPS in the setting of GI-aGVHD) expression of GI-trophic receptors (eg, β7 integrin) is induced preferentially on CD8⁺ Teff cells (vs CD4⁺ Tregs). Professional illustration by Patrick Lane, ScEYEnce Studios.