A critical function for CD200 in lung immune homeostasis and the severity of influenza infection

Abstract

The lung must maintain a high threshold of immune 'ignorance' to innocuous antigens to avoid inflammatory disease that depends on the balance of positive inflammatory signals and repressor pathways. We demonstrate here that airway macrophages had higher expression of the negative regulator CD200 receptor (CD200R) than did their systemic counterparts. Lung macrophages were restrained by CD200 expressed on airway epithelium. Mice lacking CD200 had more macrophage activity and enhanced sensitivity to influenza infection, which led to delayed resolution of inflammation and, ultimately, death. The administration of agonists that bind CD200R, however, prevented inflammatory lung disease. Thus, CD200R is critical for lung macrophage immune homeostasis in the resting state and limits inflammatory amplitude and duration during pulmonary influenza infection.

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

“…It is likely that these processes are regulated by CD200-CD200R through the same mechanism. Notably, infection of Cd200 À/À mice with Neisseria meningitides or influenza virus causes increased production of pro-inflammatory cytokines, including IL-1b, IL-6, tumor necrosis factora and interferong (Snelgrove et al, 2008;Mukhopadhyay et al, 2010). In our endogenous tumor model we also observed higher levels of the pro-inflammatory cytokines IL-1b and IL-6 in tumor-draining LN DCs derived from Cd200 À/À mice.…”

Intestinal macrophages – specialised adaptation to a unique environment

“…Steady-state intestinal Mjs express many inhibitory receptors including CD172a (SIRPa), CD200R1, IL-10R and receptors for TGF-b [10,38,39]. The ligands for each of these receptors are highly abundant in the intestine and in vitro studies have shown that some of these ligands can drive Mj differentiation into a pathway similar to that seen in the intestine.…”

Soluble CD200 Correlates With Interleukin-6 Levels in Sera of COPD Patients: Potential Implication of the CD200/CD200R Axis in the Disease Course

“…The CD200/CD200 receptor (CD200R) axis has been reported to control myeloid cell activation [9,10] and to be crucially involved in the maintenance of lung immune homeostasis [11] in both human and mice [12,13]. The CD200 molecule is expressed on airways epithelial cells, endothelial cells and T cells [9,14], whereas the CD200R molecule is predominantly expressed on airway macrophages and neutrophils [13].…”

“…The CD200 molecule is expressed on airways epithelial cells, endothelial cells and T cells [9,14], whereas the CD200R molecule is predominantly expressed on airway macrophages and neutrophils [13].…”

“…-/-mice were shown to develop excessive lung inflammation with enhanced neutrophils [23] and T lymphocytes [24] infiltration into the lung, and thereby succumb to severe tissue damage following pulmonary infection [13].…”