Figure 2. Distinct immunological programs involved in the initiation of Type-I vs. Type-II immunity.

Type-II responses (left) are elicited in response to multiple skin-derived stimuli generated due to tissue damage and cell death. Various epithelial-derived alarmins, as well as mast cell-, neuronal-, and ILC-derived signals are integrated by the local dermal cDC2s, which next migrate into LNs to induce Th2 cell differentiation at the T/B border. In contrast, Type-I inflammatory settings (right) are elicited in response to innate sensing of microbe-associated molecular patterns and downstream inflammatory cytokines. In settings of ample antigen and agonist drainage to LNs, T cell responses are primarily induced through cooperation between LN-resident cDCs and blood-derived monocytes, as well as through participation of additional innate cell types (also see Figure 1). During highly tropic infections, peripheral tissue-derived dermal cDC1 and cDC2s more dominantly promote the generation of responses. Location of early activated Th1 and Th2 T cells depends on the positioning of specific antigen-presenting cDC subsets, as well as the chemokine receptors expressed on the responding cells.

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