GM-CSF regulates lung homeostasis by promoting development of CD301b⁺ resident dendritic cells that induce regulatory T cells

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B658
Abstract ID: 5483

Presenting Author:
Christina Wilkinson , Postdoctoral Fellow at NIEHS, NIH

Abstract:

The incidence and severity of allergic inflammation of the airway is driven by the balance between allergen-specific T regulatory (Treg) and T helper (Th)2 cells, but it is not known whether different subsets of conventional dendritic cells (cDCs) promote these two T cell lineaeges. In the lung, there are two major cDC subsets, CD103⁺ cDC1 and CD11b⁺ cDC2, the latter being heterogeneous. We have identified a subset of cDC2s that predominate at baseline and display superior Treg inducing activity ex vivo. They are marked by high display of CD301b, have high expression of Csf2rb, and are responsive to the cytokine, GM-CSF. Single cell RNA sequencing and adoptive transfer experiments show that during allergic sensitization, many CD301b⁺ Treg-inducing DCs transition in a step-wise manner to Th2-inducing cDC2s that express Cd200 and Ccr7. Compared with wild-type animals, mice lacking Csf2rb in cDCs have fewer Treg-inducing CD301b⁺ cDC2s and therefore display increased inflammation in an asthma model. Additionally, mice overexpressing GM-CSF have increased CD301b⁺ cDC2s at steady state. Thus, GM-CSF maintains lung homeostasis by increasing numbers of Treg-inducing CD301b⁺ cDC2s.