Distinct dendritic cell subsets actively induce Th2 polarization

Abstract

The mechanisms by which dendritic cells induce Th2 polarization (DC(Th2) cells) have been controversial. Many have argued that DC(Th2) cells are not a distinct functional DC subset, but rather, DC-induced polarization of Th2 cells is a default pathway that occurs in the absence of inflammatory signals leading to DC-induced polarization of Th1/Th17 cells. However, recent studies demonstrate that distinct subsets of tissue DCs actively polarize Th2 cells after stimulation with type-2 inducing stimuli. DC(Th2) cells development is marked by the upregulation of specific transcription factors, cell surface molecules, and cytokines. These findings counter previous hypotheses that Th2 skewing by DCs is a passive response and support a model in which DCs are actively programmed to induce Th2 differentiation.

Figure 1

Signaling through FcRγ-associated receptors on dendritic cells drives IL-33-dependent Th2-type responses. Class I allergens (i.e. pollen, house dust mite, and pollen) have allergenic components that can act as enzymes, while Class II allergens (i.e. animal dander) do not exhibit enzymatic activity. Class I allergens contain glycans that can bind directly to Dectin-2 whereas more homogenous protein allergens like animal dander must form antigen-specific IgG immune complexes that can activate FcγRIII. Ligation of these receptors on DCs leads to signaling through FcRγ, which upregulates the transcription factor IRF4 as well as IL-33 and IL-10 to promote development of DC^Th2 cells and allergic airway inflammation.