The immunoglobulin superfamily member CD200R identifies cells involved in type 2 immune responses.

Abstract

The pathology of allergic diseases involves type 2 immune cells, such as Th2, ILC2, and basophils exerting their effect by production of IL-4, IL-5, and IL-13. However, surface receptors that are specifically expressed on type 2 immune cells are less well documented. The aim of this investigation was to identify surface markers associated with type 2 inflammation. Naïve human CD4+ T cells were short-term activated in the presence or absence of IL-4 and analyzed for expression of >300 cell-surface proteins. Ex vivo-isolated peripheral blood mononuclear cells (PBMCs) from peanut-allergic (PA) and nonallergic subjects were stimulated (14-16 h) with peanut extract to detect peanut-specific CD4+ CD154+ T cells. Biopsies were obtained for transcriptomic analysis from healthy controls and patients with extrinsic or intrinsic atopic dermatitis (AD) and psoriasis. Expression analysis of >300 surface proteins enabled identification of IL-4-upregulated surface proteins, such as CD90, CD108, CD109, and CD200R (CD200R1). Additional analysis of in vitro-differentiated Th0, Th1, and Th2 cultures identified CD200R as upregulated on Th2 cells. From ex vivo-isolated PBMCs, we found high expression of CD200R on Th2 and ILC2 cells and basophils. In PA subjects, the peanut-specific Th2 (CD154+ CRTh2+ ) cells expressed more CD200R than the non-allergen-specific Th2 (CD154- CRTh2+ ) cells. Moreover, costaining of CD161 and CD200R identified peanut-specific highly differentiated IL-4+ IL-5+ Th2 cells. Finally, transcriptomic analysis revealed upregulation of CD200R in lesional skin from subjects with an extrinsic AD phenotype compared to healthy skin. These results indicate that CD200R expression strongly correlates with Th2 pathology; though, the mechanism is as yet elusive.