Dendritic cells in Th2 immune responses and allergic sensitization

Abstract

Allergic responses are characterized by the activation of a specific subset of effector CD4 + T cells, the T-helper type 2 (Th2) cells, that respond to harmless environmental antigens causing inflammation and pathology. Th2 cells are also found in the context of parasite infections, where they can mediate parasite clearance and expulsion, and support tissue repair. The process that leads to the activation of Th2 cells in vivo is incompletely understood: while it has become clear that "conventional" dendritic cells are essential antigen-presenting cells for the initiation of Th2 immune responses, the molecules that are expressed by dendritic cells exposed to allergens, and the mediators that are produced as a consequence and signal to na€ ıve CD4 + T cells to promote their development into effector Th2, remain to be defined. Here we summarize recent developments in the identification of the dendritic cell subsets involved in Th2 responses, review potential mechanisms proposed to explain the generation of these immune responses, and discuss the direct and indirect signals that condition dendritic cells to drive the development of Th2 responses during allergen or parasite exposure.

Defined Intestinal Regions Are Drained by Specific Lymph Nodes That Mount Distinct Th1 and Th2 Responses Against Schistosoma mansoni Eggs

“…We show that in contrast to SEA and most reported Th2inducing antigens (47), which are presented by IRF4 + DC2s, intestinal BATF3-dependent CD103 + single-positive DCs (62) can also take up fluorescently labeled HES and are sufficient to induce HES-specific immune responses when transferred in vivo ( Figure 6). While the direct involvement of CD103 singlepositive DC1s in priming Th2 responses in this system requires further investigation, BATF3-dependent migratory DCs are known to suppress helminth-driven type 2 immunity in the intestine through the expression of IL-12 (63).…”

“…The involvement of DCs in the induction of type 2 immune responses against helminths is in turn better understood (47). CD11c + DCs are necessary for the induction of type 2 immune responses against S. mansoni and SEA in vivo (46) and IRF4dependent migratory DC2s are required for effective type 2 immunity in the intestine (25,48), lung (56), and skin (48,57).…”

“…CD11c + DCs are necessary for the induction of type 2 immune responses against S. mansoni and SEA in vivo (46) and IRF4dependent migratory DC2s are required for effective type 2 immunity in the intestine (25,48), lung (56), and skin (48,57). Further DC subsets that express CD301b or are dependent on KLF4 are required to drive type 2 immune responses in the skin (49,58,59) but have not been described in other tissues (47). Our comparison of type 2 immune responses after intestinal or footpad immunization of SEA (Figure 1) or HES (Figure 3) demonstrates that IL-4 + cells are more frequent and Th2associated cytokine levels are higher after restimulation in the pLN compared to the MLN, indicating that the skin represents a Th2-promoting environment, which could be influenced by skin-specific subsets of DCs.…”

“…Dendritic cells (DCs) play a crucial role in priming CD4 + T cell responses against parasite antigens (25,(46)(47)(48)(49)(50). To confirm that DCs were also responsible for the uptake of subserosally injected helminth antigens and their delivery to the individual draining MLNs, we injected fluorescently labeled AF660-SEA into the ileum, collected the individual MLNs 24 h after injection, and assessed antigen-positive cells by flow cytometry.…”

The skin environment controls local dendritic cell differentiation and function through innate IL-13

“…The DC signals that drive the development of Th2 responses remain undefined (Lamiable et al, 2020). We therefore examined the expression of several functional activation markers on DCs (Connor et al, 2014; Connor et al, 2017; Harris et al, 1999; Pellefigues et al, 2017).…”