CD200, a "no danger" signal for hair follicles

The "danger model" of immune recognition proposes that the immune system does not differentiate between self and non-self when deciding whether to mount a response, but instead, discerns between that which is dangerous or not dangerous to the host. Danger signals incite inflammatory responses, which can lead to the induction of tissue-specific autoimmunity. Immunosuppressive molecules expressed on selected cells have the potential to regulate tissue-specific inflammation, and consequently, autoimmunity. Recent studies have revealed that CD200, a potent immunoregulatory protein, is expressed on Langerhans cells (LCs) and keratinocytes (KCs) in mouse epidermis. CD200 expression is concentrated on KCs comprising the outer root sheath (ORS) of murine hair follicles (HF). Skin deficient in CD200 is highly susceptible to HF-associated inflammation and immune-mediated alopecia. In this concept review, the results of recent studies on CD200 and its inhibitory receptor, CD200R, are summarized and integrated to yield a model whereby CD200-CD200R interaction attenuates perifollicular inflammation, prevents HF-specific autoimmunity and may protect epidermal stem cells from autoimmune destruction. Further elucidation of the CD200-CD200R signaling pathway in cutaneous tissues may advance understanding of how immune homeostasis is established and maintained in the skin.