Abstract
C-C chemoattractant cytokine (chemokine) receptor 6 (CCR6) and its exclusive binding molecule CCL20 is an extremely important chemokine receptor-ligand pair which controls cell migration and immune induction during inflammatory disease. Not many scientific studies have been undertaken to study its immune mechanisms in detail, but its unique contribution to steady state cell chemotaxis in upholding immune tolerance and regulating immune homeostasis during inflammation is evident in multiple systems in the human body, including skin, liver, lung, kidney, brain, eye, joints, gonads and the gut. The role of CCR6 is constitutively expressed as a series of much debilitating severe inflammatory and autoimmune diseases, Human Immunodeficiency Virus (HIV) and cancer metastasis. CD4+ T cells, the central organizers of adaptive immunity, are stringently mobilized by the CCR6/CCL20 axis also induced by cytokines and a host of other factors in a carefully executed immune modulation scenario, to bring about a delicate balance between inflammation inducing TH17 cells and regulatory Treg cells. Although the exact immune regulatory role is not elucidated as yet, the CCR6/CCL20 axis is implicated as a front runner which determines the polarization of TH17 and regulatory Treg cells, upon which depends the resolution or progression of many debilitating disorders. This review therefore aims at emphasizing the pleiotropic significance of the chemokines CCR6 and CCL20 in immunologic function in multiple organ systems, thereby hoping to accentuate its value in future therapeutic modalities.
Highlights
ChemokinesChemokines represent an exclusive cell directing system in the body, consisting of signaling proteins vital to the immune system
Naïve T helper cells resident in lymph nodes, upon antigen sampling will differentiate into its effector sub populations, TH 17 and regulatory TH and regulatory (Treg) cells, TH 1 and TH 2, mediated by the prevailing cytokine environment and a host of other factors
CCR6 confers an antagonistic function in these T helper populations, the TH 17 and Treg cells, it is unknown what other factors are responsible for tipping the balance in favor of disease progression
Summary
Chemokines represent an exclusive cell directing system in the body, consisting of signaling proteins vital to the immune system. The best example is corroborated by the role of chemokines in mucosal immunity, where epithelial cells of the mucosa activated by an inflammatory stimulus releases the chemokine ligands, constitutively inducing chemotaxis of the leukocytes bearing their corresponding receptors towards them [1]. This is necessarily how chemokines mediate immune modulation and maintain cell migration during immune homeostasis or inflammation. Chemokine receptors function as guanine nucleotide exchange factors, mainly limited to the pertussis–toxin sensitive G1 class of G proteins Their immunological effects consist of coordinating leucocyte development, differentiation, distribution, chemotactic migration and their effector capabilities [4]. Upon synthesis within the cell, chemokines are secreted and get tethered to glycosaminoglycans, a group of sulfated polysaccharides present in the extracellular matrix or surface which constructs a steady chemokine gradient that ensures binding with its receptor [1]
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