A myriad of functions and complex regulation of the CCR7/CCL19/CCL21 chemokine axis in the adaptive immune system

Abstract

The chemokine receptor CCR7 and its ligands CCL19 and CCL21 control a diverse array of migratory events in adaptive immune function. Most prominently, CCR7 promotes homing of T cells and DCs to T cell areas of lymphoid tissues where T cell priming occurs. However, CCR7 and its ligands also contribute to a multitude of adaptive immune functions including thymocyte development, secondary lymphoid organogenesis, high affinity antibody responses, regulatory and memory T cell function, and lymphocyte egress from tissues. In this survey, we summarise the role of CCR7 in adaptive immunity and describe recent progress in understanding how this axis is regulated. In particular we highlight CCX-CKR, which scavenges both CCR7 ligands, and discuss its emerging significance in the immune system.

Keywords: APC; B cell receptor; BCR; CC chemokine ligand; CC chemokine receptor; CCL; CCL19; CCL21; CCR; CCR7; CMJ; CNS; CXC chemokine ligand; CXC chemokine receptor; CXCL; CXCR; Chemokine; DN; EAE; FRC; G-protein coupled receptor; GAG; GC; GPCR; HEV; Immunity; KO; LCMV; LEC; LN; LT; LTi; MAdCAM-1; MHC; MZ; PALS; PGE2; PNAd; PP; Peyer's patch; S1P1; SCS; SLO; SP; T cell receptor; T follicular helper cell; T(CM); T(FH); T(REG); TCR; TEC; TLO; VEGF; VSV; VV; antigen-presenting cell; central memory T cell; central nervous system; cortico-medullary junction; double negative; experimental autoimmune encephalomyelitis; fibroblastic reticular cell; germinal centre; glycosaminoglycan; high endothelial venule; knock out; lymph node; lymphatic endothelial cell; lymphochorio meningitis virus; lymphoid tissue inducer; lymphotoxin; major histocompatibility complex; marginal zone; mucosal addressin cell adhesion molecule 1; paucity of lymph node T cells; periartiolar lymphoid sheath; peripheral node addressin; plt; prostaglandin E2; regulatory T cell; secondary lymphoid organ; single positive; sphingosine-1-phosphate receptor; subcapsular sinus; tertiary lymphoid organ; thymic epithelial cell; vaccinia virus; vascular endothelial growth factor; vesicular stromatitis virus.