Influence of cytokines on gut immune homeostasis

Neutrophil recruitment to the intestinal lamina propria in the early stages of inflammation is induced by IL-8, a chemokine secreted by macrophages and epithelial cells. Antigen-presenting cells including DCs and macrophages drive T helper cell (Th1), Th9, Th17, or Th2 differentiation through the secretion of IL-12 (Th1) or IL-23, IL-6, transforming growth factor (TGF)-beta, IL1 beta (Th17 or Th9 per specific combination of cytokines), or IL-4 (Th2). Epithelial cells can also secrete cytokines such as IL-33 and TSLP that can contribute to Th2 differentiation. T effector cells secrete pro-inflammatory cytokines that lead to inflammation. CD1d-restricted natural killer (NK) T cells secrete IL-13 upon activation and lead to Th2 cytokine secretion. Suppression of inflammation can occur through naturally occurring thymic-derived Foxp3+ regulatory cells (Foxp3+ Treg), IL-10 producing T cells (Tr1), or TGF-beta secreting T cells (Th3). Suppressive Foxp3+ T cells can also arise from Foxp3– T cells upon retinoic acid and TGF-beta stimulation via CD103+ DCs. T-bet, GATA-3, PU.1, ROR-gamma-t, and Foxp3 are transcription factors involved in Th1, Th2, Th9, Th17, and Treg differentiation, respectively.