Chemokine phenotypes

Among the known chemokine receptors, CXCR4 has been established to play a crucial role in the nervous system physiology as evidenced by either CXCL12 or CXCR4 homozygous mutants phenotype (Ma et al. 1998 Zou et al. 1998). The other receptors discussed in this review are primarily involved in inflammatory and/ or neurodegenerative disorders which is consistent with their roles as inflammatory chemokines. 

Fig. 1. Surface phenotype of HSPCs. Primitive HSPCs have the phenotype of c-KitThy-ll0WLin CD34+CD33 in humans, and the mouse counterparts have the phenotype of c-KifThy-llowLin Sca-l+. Primitive HSPCs express CXCR4 as the major chemokine receptor and various adhesion molecules such as VLA-4, VLA-5, LFA-1, P-selectin glycoprotein ligand-1 (PSGL-1), and CD44 for migration to the stem cell niche.

Sato N, Ahuja SK, Quinones M, et al. CC chemokine receptor (CCR)2 is required for langerhans cell migration and localization of T helper cell type 1 (Thl)-inducing dendritic cells. Absence of CCR2 shifts the Leishmania major-resistant phenotype to a susceptible state dominated by Th2 cytokines, b cell outgrowth, and sustained neutrophilic inflammation. J Exp Med 2000 192(2) 205-218. 

Wang J, Hunt JL, Gooding W, et al. Expression pattern of chemokine receptor 6 (CCR6) and CCR7 in squamous cell carcinoma of the head and neck identifies a novel metastatic phenotype. Cancer Res 2004 64 1861-1866. 

Fig. 14.1. The Thl/Th2 balance is central to the regulation of normal wound repair. Tissue injury results in the initiation of an inflammatory response, mediated by a variety of cells and their by-products. Immune cells are recruited and cross-regulate the Thl/ Th2 balance that occurs in response to the cytokine environment. This balance is in turn cross-regulated by the chemokine/chemokine-receptor expression profile, which functions to amplify the inflammatory process. Cells residing in the injured tissue release profibrotic mediators, which promote fibroblast activation, proliferation, and differentiation to the myofibroblast phenotype. Myofibroblasts produce collagen to repair damaged tissue, which is an event that is favored by the inhibition of MMP activity. The Thl/Th2 balance is central to whether a normal or aberrant wound-repair process is established A Thl environment promotes normal tissue resolution (fibrinolysis), whereas a Th2 environment maintains the progression of fibrotic disease (excessive collagen deposition).

---