Reduced cutaneous CD200:CD200R1 signalling in psoriasis enhances neutrophil recruitment to skin

Holly Linley, Shafqat Jaigirdar, Karishma Mohamed, C. E. M. Griffiths, Amy Saunders

Research output: Contribution to journalArticlepeer-review


The skin immune system is tightly regulated to prevent inappropriate inflammation in response to harmless environmental substances. This regulation is actively maintained by mechanisms including cytokines and cell surface receptors and its loss results in inflammatory disease. In the case of psoriasis, inappropriate immune activation leads to IL-17-driven chronic inflammation, but molecular mechanisms underlying this loss of regulation are not well understood. Immunoglobulin family member CD200 and its receptor, CD200R1, are important regulators of inflammation. Therefore we determined if this pathway is dysregulated in psoriasis, and how this affects immune cell activity.
Human skin biopsies were examined by QPCR, flow cytometry, and immunohistochemistry. The role of CD200R1 in regulating psoriasis-like skin inflammation was examined using CD200R1 blocking antibodies in mouse psoriasis models. CD200R1 blocking antibodies were also used in an in vivo neutrophil recruitment assay and in in vitro assays to examine macrophage, innate lymphoid cell,  T cell and neutrophil activity.
We reveal that CD200 and signalling via CD200R1 are reduced in non-lesional psoriasis skin. In mouse models of psoriasis CD200R1 was shown to limit psoriasislike inflammation by enhancing acanthosis, CCL20 production and neutrophil recruitment, but surprisingly, macrophage function and IL-17 production were not affected, and neutrophil reactive oxygen species production was reduced.
Collectively, these data show that CD200R1 affects neutrophil function and limits inflammatory responses in healthy skin by restricting neutrophil recruitment. However, the CD200 pathway is reduced in psoriasis, resulting in a loss of immune control, and increased neutrophil recruitment in mouse models. In conclusion, we highlight CD200R1:CD200 as a pathway that might be targeted to dampen inflammation in patients with psoriasis.
Original languageEnglish
JournalImmunity Inflammation and Disease
Publication statusAccepted/In press - 11 May 2022


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