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

Abstract

Background

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.

Methods

Naïve human CD4⁺ T-cells were short-term activated in the presence or absence of IL-4, and analysed for expression of >300 cell-surface proteins. Ex vivo isolated PBMCs from peanut and non-allergic allergic subjects, were stimulated (14-16h) 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 and psoriasis.

Results

Expression analysis of >300 surface proteins enabled identification of IL-4 up-regulated surface proteins, such as CD90, CD108, CD109, and CD200R (CD200R1). Additional analysis of in vitro differentiated Th0, Th1, and Th2 cultures, identified CD200R as up-regulated on Th2 cells. From ex vivo isolated PBMCs, we found high expression of CD200R on Th2 and ILC2 cells and basophils. In peanut-allergic subjects the peanut-specific Th2 (CD154⁺CRTh2⁺) cells expressed more CD200R than the non-allergen specific Th2 (CD154^-CRTh2⁺) cells. Moreover, co-staining of CD161 and CD200R identified peanut-specific highly differentiated IL-4⁺IL-5⁺ Th2 cells. Finally, transcriptomic analysis revealed up-regulation of CD200R in lesional skin from subjects with an extrinsic atopic dermatitis phenotype compared to healthy skin.

Conclusion

These results indicate that CD200R expression strongly correlates with Th2 pathology; though, the mechanism is as yet elusive.

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