Expression of CD200 on Epithelial Cells of the Murine Hair Follicle: A Role in Tissue-Specific Immune Tolerance?

Abstract

CD200 (OX-2) is a transmembrane glycoprotein that transmits an immunoregulatory signal through the CD200 receptor (CD200R) to attenuate inflammatory reactions and promote immune tolerance. CD200 expression in the skin has not been described previously. We now report that freshly isolated cells of the murine epidermis contain a subpopulation of major histocompatibility complex (MHC) class II-negative, CD3-negative keratinocytes that are CD200-positive. CD200 expression was accentuated in keratinocytes comprising the outer root sheath of the murine hair follicle (HF). When syngeneic skin grafts were exchanged between gender-matched wild-type (WT) and CD200-deficient C57BL/6 mice, significant perifollicular and intrafollicular inflammation was observed, eventually leading to the destruction of virtually all HF (alopecia) without significant loss of the CD200-negative grafts. Minimal and transient inflammation was observed in WT grafts, which persisted long term with hair. There was a 2-fold increase in graft-infiltrating T cells in CD200-deficient skin at 14 d. Alopecia and skin lesions were induced in CD200-deficient hosts by adoptive transfer of splenocytes from WT mice previously grafted with CD200-negative skin, but not from mice grafted with WT skin. Collectively, these results suggest that the expression of CD200 in follicular epithelium attenuates inflammatory reactions and may play a role in maintaining immune tolerance to HF-associated autoantigens.

Constrained release of lamina-associated enhancers and genes from the nuclear envelope during T-cell activation facilitates their association in chromosome compartments

“…See also Supplemental Figure S7. 2009; Wallner et al 2012). Consistent with these important regulatory activities, the dysregulation or loss of function of a number of these peripherally regulated gene products is associated with autoimmunity (Watanabe et al 2003;Rosenblum et al 2004;Sharma et al 2011;Wallner et al 2012;Johansen et al 2015;Hussman et al 2016). Thus, in all cases, the tighter regulation of these genes in resting lymphocytes from adding spatial control would benefit the organism.…”

CD200-CD200R signaling suppresses anti-tumor responses independently of CD200 expression on the tumor

“…Non-hematopoietic cells may deliver the initial CD200 signal, after which CD200 on T-cells could provide a feedback loop for the maintenance of tolerance. Expression of CD200 on hair follicle cells attenuates skin inflammation and enhances skin-graft survival (Gorczynski et al, 1999;Rosenblum et al, 2004). An inhibitory feedback loop between tolerogenic DC and Treg cells has been proposed previously and it is interesting to speculate on a role for CD200-CD200R herein (Min et al, 2003).…”

Co-expression of the toleragenic glycoprotein, CD200, with markers for cancer stem cells

“…There is an impressive body of evidence implicating CD200-CD200R interactions on immune tolerance, transplantation, autoimmunity and therapy [23][24][25]. Notably, CD200-deficient mice develop a number of autoimmune disorders including experimental allergic encephalomyelitis, collagen-induced arthritis, and autoimmune alopecia [23;24].…”