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The immunoglobulin superfamily member CD 200R identifies cells involved in type 2 immune responses
Author(s) -
Blom L. H.,
Martel B. C.,
Larsen L. F.,
Hansen C. V.,
Christensen M. P.,
JuelBerg N.,
Litman T.,
Poulsen L. K.
Publication year - 2017
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13129
Subject(s) - immune system , peripheral blood mononuclear cell , biology , immunology , ex vivo , antibody , downregulation and upregulation , microbiology and biotechnology , chemistry , in vitro , biochemistry , gene
Background The pathology of allergic diseases involves type 2 immune cells, such as Th2, ILC 2, 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 CD 4 + 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 ( PBMC s) from peanut‐allergic ( PA ) and nonallergic subjects were stimulated (14–16 h) with peanut extract to detect peanut‐specific CD 4 + CD 154 + T cells. Biopsies were obtained for transcriptomic analysis from healthy controls and patients with extrinsic or intrinsic atopic dermatitis (AD) and psoriasis. Results Expression analysis of >300 surface proteins enabled identification of IL ‐4‐upregulated surface proteins, such as CD 90, CD 108, CD 109, and CD 200R ( CD 200R1). Additional analysis of in vitro ‐differentiated Th0, Th1, and Th2 cultures identified CD 200R as upregulated on Th2 cells. From ex vivo ‐isolated PBMC s, we found high expression of CD 200R on Th2 and ILC 2 cells and basophils. In PA subjects, the peanut‐specific Th2 ( CD 154 + CRT h2 + ) cells expressed more CD 200R than the non‐allergen‐specific Th2 ( CD 154 − CRT h2 + ) cells. Moreover, costaining of CD 161 and CD 200R identified peanut‐specific highly differentiated IL ‐4 + IL ‐5 + Th2 cells. Finally, transcriptomic analysis revealed upregulation of CD 200R in lesional skin from subjects with an extrinsic AD phenotype compared to healthy skin. Conclusion These results indicate that CD 200R expression strongly correlates with Th2 pathology; though, the mechanism is as yet elusive.