Fig. 3 |. Specialized functions of mouse classical dendritic cell subsets.

Type 1 classical dendritic cells (cDC1s) are specialized in the regulation of type I immune responses through the priming and activation of cytotoxic CD8⁺ T cells and CD4⁺ T helper 1 (T_H1) cells. Relative to other DC subsets, cDC1s specifically express Toll-like receptor 3 (TLR3) and TLR11, which recognize double-stranded RNA (dsRNA) and the Toxoplasma gondii antigen profilin, respectively. cDC1s are an essential source of IL-12 and are necessary for resistance to intracellular viral, bacterial and parasitic infections. cDC1s are uniquely capable of acquiring antigens associated with host cells, through a process known as cross-presentation, which is essential for pathogen clearance and antitumour immune responses. Type 2 classical dendritic cells (cDC2s) regulate type II and type III immune responses and antibody responses to soluble antigens. cDC2s at barrier surfaces, such as in the lung, gut and skin, regulate type II immune responses to parasites, fungi and allergens and are required for the expansion of CD4⁺ T helper 2 (T_H2) cell populations and activation of group 2 innate lymphoid cells (ILC2s). The regulation of such responses depends on cDC-intrinsic expression of interferon regulatory factor 4 (Irf4) and has been attributed to the Klf4-dependent cDC2 subset. Type III immune responses are regulated by a distinct subset of Notch 2-dependent cDCs, which are a necessary source of IL-23 during acute infection with Citrobacter rodentium. IL-23 is necessary to activate group 3 innate lymphoid cells (ILC3s) and to induce differentiation of CD4⁺ T helper 17 (T_H17) cells. cDC2s have also been shown to regulate antibody responses though the induction of germinal centre responses to soluble antigens in lymphoid organs. Deficiency in Notch2-dependent cDCs results in a failure to induce CD4⁺ T follicular helper (T_FH) cells and germinal centre B cells in the spleen, for example. TCR, T cell receptor.