Figure 1 Mucosal immune networks

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Figure 1 Mucosal immune networks Figure 1 | Mucosal immune networks. The mucosal immune system has a crucial role in immunity to microorganisms and in epithelial restitution. Distinct arms of host immunity can be mobilized to defend against specific microbial threats. However, selective aspects of these immune response pathways can be inappropriately deployed in immune-mediated diseases. T-Bet-expressing type 1 T helper (TH1) effector memory T-cells and type 1 innate lymphoid cells (ILCs) respond to cytokine signals (including IL-12) to trigger their effector responses, which includes production of IFNγ, which in turn primes tissue mononuclear phagocytes, such as macrophages and monocytes, programming them for pro-inflammatory activation. This pathway is especially important in host resistance to intracellular bacteria, including mycobacterial infection. IL-12-producing M1 macrophages support the type 1 inflammatory response, and reciprocally IFNγ supports M1 differentiation. The type 2 response is characterized by activation of GATA3-expressing type 2 T helper (TH2) cells and ILC2, which produce cytokines (such as IL-4, IL-5 and IL-13) to support the activation, recruitment and survival of eosinophils and mast cells. The type 2 response is implicated in host resistance to helminths. RORγt-expressing type 17 T helper (TH17) and ILC3 (especially natural cytotoxicity receptor (NCR)− ILC3) cells produce IL-17 family cytokines, which support the activation and recruitment of neutrophils and have an important role in host immunity to extracellular bacteria and fungi. NCR+ ILC3 produce IL22, which supports the epithelial stem cell niche by promoting proliferation of LGR5+ stem cells and also promote the production of antimicrobial peptides by epithelial cells. IL-22-producing ILC3 are implicated in host resistance to some mucosal pathogens. Powell, N. et al. (2017) The mucosal immune system: master regulator of bidirectional gut–brain communications Nat. Rev. Gastroenterol. Hepatol. doi:10.1038/nrgastro.2016.191