Genomes and Genes
Gene Symbol: Ccl21a
Description: chemokine (C-C motif) ligand 21A (serine)
Alias: 6CKBAC2, 6Ckine, ALP, AW987545, CKb9, SCYA21a, SLC, Scya21, Scya21b, Tca4, plt, C-C motif chemokine 21a, CC chemokine 6Ckine-ser, CCL21-Ser, beta-chemokine exodus-2, exodus-2, small inducible cytokine A21a, thymus-derived chemotactic agent 4
- Hromas R, Kim C, Klemsz M, Krathwohl M, Fife K, Cooper S, et al. Isolation and characterization of Exodus-2, a novel C-C chemokine with a unique 37-amino acid carboxyl-terminal extension. J Immunol. 1997;159:2554-8 pubmed..The combination of these characteristics may be a functional correlate for the unique carboxyl-terminal structure of Exodus-2. ..
- Wigle J, Harvey N, Detmar M, Lagutina I, Grosveld G, Gunn M, et al. An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype. EMBO J. 2002;21:1505-13 pubmed..wild-type embryos, those of Prox1-null embryos did not co-express any lymphatic markers such as VEGFR-3, LYVE-1 or SLC. Instead, the mutant cells appeared to have a blood vascular phenotype, as determined by their expression of ..
- Nakano H, Tamura T, Yoshimoto T, Yagita H, Miyasaka M, Butcher E, et al. Genetic defect in T lymphocyte-specific homing into peripheral lymph nodes. Eur J Immunol. 1997;27:215-21 pubmed..the defect in T cell-specific homing was regulated by a single autosomal recessive gene, tentatively designated plt (paucity of lymph node T cells)...
- Britschgi M, Favre S, Luther S. CCL21 is sufficient to mediate DC migration, maturation and function in the absence of CCL19. Eur J Immunol. 2010;40:1266-71 pubmed publisher..Our findings suggest that CCL21 is the critical CCR7 ligand regulating DC homeostasis and function in vivo with CCL19 being redundant for these processes. ..
- Luther S, Ansel K, Cyster J. Overlapping roles of CXCL13, interleukin 7 receptor alpha, and CCR7 ligands in lymph node development. J Exp Med. 2003;197:1191-8 pubmed..Using CXCL13-/- mice that additionally carry the paucity of LN T cell mutation (plt/plt), we discovered that CCR7 ligands function in peripheral LN development...
- Luther S, Bidgol A, Hargreaves D, Schmidt A, Xu Y, Paniyadi J, et al. Differing activities of homeostatic chemokines CCL19, CCL21, and CXCL12 in lymphocyte and dendritic cell recruitment and lymphoid neogenesis. J Immunol. 2002;169:424-33 pubmed
- Bleul C, Boehm T. Chemokines define distinct microenvironments in the developing thymus. Eur J Immunol. 2000;30:3371-9 pubmed..chemokines is regulated temporally during embryogenesis; in the alymphoid early thymic anlage, only TECK, SDF-1 and SLC but not ELC, MDC or TARC are expressed...
- Nakano H, Mori S, Yonekawa H, Nariuchi H, Matsuzawa A, Kakiuchi T. A novel mutant gene involved in T-lymphocyte-specific homing into peripheral lymphoid organs on mouse chromosome 4. Blood. 1998;91:2886-95 pubmed..shown a mutant mouse DDD/1 with T-cell-specific homing defect that is regulated by an autosomal recessive gene, plt (paucity of lymph node T cells), and seems to be caused by lymph node (LN) stromal cells...
- Kurobe H, Liu C, Ueno T, Saito F, Ohigashi I, Seach N, et al. CCR7-dependent cortex-to-medulla migration of positively selected thymocytes is essential for establishing central tolerance. Immunity. 2006;24:165-77 pubmed..These results indicate that CCR7-mediated cortex-to-medulla migration of thymocytes is essential for establishing central tolerance rather than for supporting the maturation or export of thymocytes. ..
- Gunn M, Kyuwa S, Tam C, Kakiuchi T, Matsuzawa A, Williams L, et al. Mice lacking expression of secondary lymphoid organ chemokine have defects in lymphocyte homing and dendritic cell localization. J Exp Med. 1999;189:451-60 pubmedSecondary lymphoid organ chemokine (SLC) is expressed in high endothelial venules and in T cell zones of spleen and lymph nodes (LNs) and strongly attracts naive T cells...
- Gunn M, Tangemann K, Tam C, Cyster J, Rosen S, Williams L. A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of naive T lymphocytes. Proc Natl Acad Sci U S A. 1998;95:258-63 pubmed..Here we show that a chemokine represented in the EST database, secondary lymphoid-tissue chemokine (SLC), is expressed in the high endothelial venules of lymph nodes and Peyer's patches, in the T cell areas of spleen, ..
- Stein J, Rot A, Luo Y, Narasimhaswamy M, Nakano H, Gunn M, et al. The CC chemokine thymus-derived chemotactic agent 4 (TCA-4, secondary lymphoid tissue chemokine, 6Ckine, exodus-2) triggers lymphocyte function-associated antigen 1-mediated arrest of rolling T lymphocytes in peripheral lymph node high endothelial ve. J Exp Med. 2000;191:61-76 pubmed..of murine PLNs to study the role of thymus-derived chemotactic agent (TCA)-4 (secondary lymphoid tissue chemokine, 6Ckine, Exodus-2) in homing of adoptively transferred T cells from T-GFP mice, a transgenic strain that expresses green ..
- Kar U, Srivastava M, Andersson A, Baratelli F, Huang M, Kickhoefer V, et al. Novel CCL21-vault nanocapsule intratumoral delivery inhibits lung cancer growth. PLoS ONE. 2011;6:e18758 pubmed publisher..The vault nanocapsule can serve as an "off the shelf" approach to deliver antitumor cytokines to treat a broad range of malignancies. ..
- Mori S, Nakano H, Aritomi K, Wang C, Gunn M, Kakiuchi T. Mice lacking expression of the chemokines CCL21-ser and CCL19 (plt mice) demonstrate delayed but enhanced T cell immune responses. J Exp Med. 2001;193:207-18 pubmedThe paucity of lymph node T cells (plt) mutation leads to a loss of CCL21 and CCL19 expression in secondary lymphoid organs...
- Schmitz K, Pickert G, Wijnvoord N, Häussler A, Tegeder I. Dichotomy of CCL21 and CXCR3 in nerve injury-evoked and autoimmunity-evoked hyperalgesia. Brain Behav Immun. 2013;32:186-200 pubmed publisher..By using the respective knockout mice we show that deficiency of CCL19/21 in plt/plt mice attenuates nerve injury evoked pain but not the hyperalgesia evoked by autoimmune encephalomyelitis (EAE)...
- Montresor A, Bolomini Vittori M, Toffali L, Rossi B, Constantin G, Laudanna C. JAK tyrosine kinases promote hierarchical activation of Rho and Rap modules of integrin activation. J Cell Biol. 2013;203:1003-19 pubmed publisher..Thus, JAK tyrosine kinases control integrin activation and dependent lymphocyte trafficking by bridging chemokine receptors to the concurrent and hierarchical activation of the Rho and Rap modules of integrin activation. ..
- Russo E, Teijeira A, Vaahtomeri K, Willrodt A, Bloch J, NitschkÃ© M, et al. Intralymphatic CCL21 Promotes Tissue Egress of Dendritic Cells through Afferent Lymphatic Vessels. Cell Rep. 2016;14:1723-1734 pubmed publisher..These findings reveal a role for intralymphatic CCL21 in promoting DC trafficking to dLNs, through the formation of a flow-induced gradient. ..
- Hromas R, Broxmeyer H, Kim C, Christopherson K, Hou Y. Isolation of ALP, a novel divergent murine CC chemokine with a unique carboxy terminal extension. Biochem Biophys Res Commun. 1999;258:737-40 pubmed..We report here, the isolation of a novel murine CC chemokine termed ALP for its amino terminal peptide sequence...
- Okada T, Miller M, Parker I, Krummel M, Neighbors M, Hartley S, et al. Antigen-engaged B cells undergo chemotaxis toward the T zone and form motile conjugates with helper T cells. PLoS Biol. 2005;3:e150 pubmed..These findings provide evidence of lymphocyte chemotaxis in vivo, and they begin to define the spatiotemporal cellular dynamics associated with T cell-dependent antibody responses. ..
- Van Zwam M, Wierenga Wolf A, Melief M, Schrijver B, Laman J, Boven L. Myelin ingestion by macrophages promotes their motility and capacity to recruit myeloid cells. J Neuroimmunol. 2010;225:112-7 pubmed publisher..Our data demonstrate that myelin-laden macrophages have increased motility and suggest trafficking between anatomical compartments in vivo. ..
- Norrmen C, Ivanov K, Cheng J, Zangger N, Delorenzi M, Jaquet M, et al. FOXC2 controls formation and maturation of lymphatic collecting vessels through cooperation with NFATc1. J Cell Biol. 2009;185:439-57 pubmed publisher..As damage to collecting vessels is a major cause of lymphatic dysfunction in humans, our results suggest that FOXC2 and NFATc1 are potential targets for therapeutic intervention. ..
- Obata Y, Kimura S, Nakato G, Iizuka K, Miyagawa Y, Nakamura Y, et al. Epithelial-stromal interaction via Notch signaling is essential for the full maturation of gut-associated lymphoid tissues. EMBO Rep. 2014;15:1297-304 pubmed publisher..These data demonstrate that epithelial Notch signaling maintained by stromal cells contributes to the full maturation of GALT by restricting secretory cell differentiation in FAE. ..
- Yanagawa Y, Onoe K. CCL19 induces rapid dendritic extension of murine dendritic cells. Blood. 2002;100:1948-56 pubmed..These findings suggest that Rac or Cdc42 (or both), but not Rho, are involved in the CCL19-induced dendritic extension of mature DCs. ..
- Kozai M, Kubo Y, Katakai T, Kondo H, Kiyonari H, Schaeuble K, et al. Essential role of CCL21 in establishment of central self-tolerance in T cells. J Exp Med. 2017;214:1925-1935 pubmed publisher..These results indicate a nonredundant role of CCL21Ser in the establishment of self-tolerance in T cells in the thymic medulla, and reveal a functional inequality among CCR7 ligands in vivo. ..
- Ismailoglu I, Yeamans G, Daley G, Perlingeiro R, Kyba M. Mesodermal patterning activity of SCL. Exp Hematol. 2008;36:1593-603 pubmed publisher..These data support a master-regulatory role for SCL in mesodermal patterning, in addition to its established later roles in hematopoietic differentiation. ..
- Weber M, Hauschild R, Schwarz J, Moussion C, de Vries I, Legler D, et al. Interstitial dendritic cell guidance by haptotactic chemokine gradients. Science. 2013;339:328-32 pubmed publisher..These findings functionally establish the concept of haptotaxis, directed migration along immobilized gradients, in tissues. ..
- Tal O, Lim H, Gurevich I, Milo I, Shipony Z, Ng L, et al. DC mobilization from the skin requires docking to immobilized CCL21 on lymphatic endothelium and intralymphatic crawling. J Exp Med. 2011;208:2141-53 pubmed publisher..Intralymphatic crawling, in which DCs combine active adhesion-based migration and directional cues from lymph flow, represents a new step in DC mobilization which may be amenable to regulation. ..
- Bénézech C, White A, Mader E, Serre K, Parnell S, Pfeffer K, et al. Ontogeny of stromal organizer cells during lymph node development. J Immunol. 2010;184:4521-30 pubmed publisher..Taken together, these results highlight the importance of the signals and cellular interactions that induce the maturation of stromal cells and ultimately lead to the formation of lymphoid tissues. ..
- Weninger W, Carlsen H, Goodarzi M, Moazed F, Crowley M, Baekkevold E, et al. Naive T cell recruitment to nonlymphoid tissues: a role for endothelium-expressed CC chemokine ligand 21 in autoimmune disease and lymphoid neogenesis. J Immunol. 2003;170:4638-48 pubmed
- Ueno T, Saito F, Gray D, Kuse S, Hieshima K, Nakano H, et al. CCR7 signals are essential for cortex-medulla migration of developing thymocytes. J Exp Med. 2004;200:493-505 pubmed..CCR7-dependent cortex-medulla migration of thymocytes plays a crucial role in medulla formation and neonatal T cell export but is not essential for maturation, survival, negative selection, and adult export of thymocytes. ..
- Hua J, Stevenson W, Dohlman T, Inomata T, Tahvildari M, Calcagno N, et al. Graft Site Microenvironment Determines Dendritic Cell Trafficking Through the CCR7-CCL19/21 Axis. Invest Ophthalmol Vis Sci. 2016;57:1457-67 pubmed publisher..We conclude that the graft site microenvironment plays a critical role in alloimmunity by determining DC trafficking through the CCR7-CCL19/21 axis. ..
- Rappert A, Biber K, Nolte C, Lipp M, Schubel A, Lu B, et al. Secondary lymphoid tissue chemokine (CCL21) activates CXCR3 to trigger a Cl- current and chemotaxis in murine microglia. J Immunol. 2002;168:3221-6 pubmed
- Nykänen A, Sandelin H, Krebs R, Keränen M, Tuuminen R, Karpanen T, et al. Targeting lymphatic vessel activation and CCL21 production by vascular endothelial growth factor receptor-3 inhibition has novel immunomodulatory and antiarteriosclerotic effects in cardiac allografts. Circulation. 2010;121:1413-22 pubmed publisher
- Junt T, Nakano H, Dumrese T, Kakiuchi T, Odermatt B, Zinkernagel R, et al. Antiviral immune responses in the absence of organized lymphoid T cell zones in plt/plt mice. J Immunol. 2002;168:6032-40 pubmedThe paucity of lymph node (LN) T cells (plt) mutation in mice results in strongly reduced T cell numbers in LNs and homing defects of both dendritic cells (DCs) and naive T cells...
- Yanagawa Y, Onoe K. CCR7 ligands induce rapid endocytosis in mature dendritic cells with concomitant up-regulation of Cdc42 and Rac activities. Blood. 2003;101:4923-9 pubmed..These findings demonstrate that certain chemokines induce rapid endocytosis in each relevant DC population. It is suggested that CCR7 ligands activate Cdc42 and Rac, thereby inducing the endocytosis in mature DCs. ..
- Yoshino M, Yamazaki H, Nakano H, Kakiuchi T, Ryoke K, Kunisada T, et al. Distinct antigen trafficking from skin in the steady and active states. Int Immunol. 2003;15:773-9 pubmed..of antigen trafficking into regional lymph nodes (LN) in CCL21-Ser-deficient paucity of lymph node T cells (plt) mice in the active state induced by lipopolysaccharide injection, corresponding with previous reports, but normal ..
- van de Pavert S, Olivier B, Goverse G, Vondenhoff M, Greuter M, Beke P, et al. Chemokine CXCL13 is essential for lymph node initiation and is induced by retinoic acid and neuronal stimulation. Nat Immunol. 2009;10:1193-9 pubmed publisher..Therefore, our data show that the initiation of lymph node development is controlled by RA-mediated expression of CXCL13 and suggest that RA may be provided by adjacent neurons. ..
- Misslitz A, Pabst O, Hintzen G, Ohl L, Kremmer E, Petrie H, et al. Thymic T cell development and progenitor localization depend on CCR7. J Exp Med. 2004;200:481-91 pubmed..Thus, our findings establish an essential role for CCR7 in intrathymic migration and proper T cell development. ..
- Brennan J, Karl J, Capel B. Divergent vascular mechanisms downstream of Sry establish the arterial system in the XY gonad. Dev Biol. 2002;244:418-28 pubmed..This newly formed arterial system establishes a new pattern of blood flow in the XY gonad, which we speculate may have an important role in export of testosterone to masculinize the XY embryo. ..
- Mikulski Z, Johnson R, Shaked I, Kim G, Nowyhed H, Goodman W, et al. SAMP1/YitFc mice develop ileitis via loss of CCL21 and defects in dendritic cell migration. Gastroenterology. 2015;148:783-793.e5 pubmed publisher..Loss of CCL21 signaling and DC migration is required for development of ileitis in SAMP mice. Reagents such as R848, which activate DC migration to the MLN, may be developed as treatments for patients with Crohn's disease. ..
- Kabashima K, Banks T, Ansel K, Lu T, Ware C, Cyster J. Intrinsic lymphotoxin-beta receptor requirement for homeostasis of lymphoid tissue dendritic cells. Immunity. 2005;22:439-50 pubmed..We conclude that LT alpha 1 bet a2 acts on DCs or DC precursors to promote DC homeostasis, and we suggest that DC proliferation is an important pathway for locally maintaining these cells in the steady state. ..
- Liu C, Ueno T, Kuse S, Saito F, Nitta T, Piali L, et al. The role of CCL21 in recruitment of T-precursor cells to fetal thymi. Blood. 2005;105:31-9 pubmed..Fetal thymus colonization was partially defective in CCL21-deficient plt/plt mice and was further diminished by anti-CCL25 antibody...
- Choi B, Lim H, Lee E, Anower A, Sohn S. CCL21 attenuates HSV-induced inflammation through up-regulation of CD8+ memory cells. Immunobiology. 2013;218:579-90 pubmed publisher..These results suggest that CCR7, its ligand, and CD8+ memory cells are correlated with the regulation of BD symptoms. ..
- Zuklys S, Gill J, Keller M, Hauri Hohl M, Zhanybekova S, Balciunaite G, et al. Stabilized beta-catenin in thymic epithelial cells blocks thymus development and function. J Immunol. 2009;182:2997-3007 pubmed publisher..These results suggest that a precise regulation of canonical Wnt signaling in thymic epithelia is essential for normal thymus development and function. ..
- Lo J, Chin R, Lee Y, Kang H, Wang Y, Weinstock J, et al. Differential regulation of CCL21 in lymphoid/nonlymphoid tissues for effectively attracting T cells to peripheral tissues. J Clin Invest. 2003;112:1495-505 pubmed..This differential regulation is due to the selective regulation of the CCL21-Ser/CCL21a but not the CCL21-Leu/CCL21b gene by the LT and noncanonical NF-kappaB pathways...
- Finsen A, Ueland T, Sjaastad I, Ranheim T, Ahmed M, Dahl C, et al. The homeostatic chemokine CCL21 predicts mortality in aortic stenosis patients and modulates left ventricular remodeling. PLoS ONE. 2014;9:e112172 pubmed publisher..Our studies, combining experiments in clinical and experimental LV pressure overload, suggest that CCL21/CCR7 interactions might be involved in the response to pressure overload secondary to AS. ..
- Kuwabara T, Ishikawa F, Yasuda T, Aritomi K, Nakano H, Tanaka Y, et al. CCR7 ligands are required for development of experimental autoimmune encephalomyelitis through generating IL-23-dependent Th17 cells. J Immunol. 2009;183:2513-21 pubmed publisher..We examined the role of these chemokines in inducing EAE. C57BL/6 mice lacking expression of these chemokines (plt/plt mice) or their receptor CCR7 were resistant to EAE induced with myelin oligodendrocyte glycoprotein peptide 35-..
- Comerford I, Nibbs R, Litchfield W, Bunting M, Harata Lee Y, Haylock Jacobs S, et al. The atypical chemokine receptor CCX-CKR scavenges homeostatic chemokines in circulation and tissues and suppresses Th17 responses. Blood. 2010;116:4130-40 pubmed publisher..Thus, by regulating homeostatic chemokine bioavailability, CCX-CKR influences the localization, kinetics, and nature of adaptive immune responses in vivo. ..
- Miyagaki T, Sugaya M, Okochi H, Asano Y, Tada Y, Kadono T, et al. Blocking MAPK signaling downregulates CCL21 in lymphatic endothelial cells and impairs contact hypersensitivity responses. J Invest Dermatol. 2011;131:1927-35 pubmed publisher..In summary, these results suggest that the MAPK pathway is important for CCL21 expression by LECs in vitro and in vivo. Blocking MAPK signaling within skin may offer a novel approach to treatment of inflammatory skin diseases. ..
- Ulvmar M, Werth K, Braun A, Kelay P, Hub E, Eller K, et al. The atypical chemokine receptor CCRL1 shapes functional CCL21 gradients in lymph nodes. Nat Immunol. 2014;15:623-30 pubmed publisher..In vitro live imaging revealed that spatially confined expression of CCRL1 was necessary and sufficient for the creation of functional chemokine gradients. ..
- Okada T, Ngo V, Ekland E, Forster R, Lipp M, Littman D, et al. Chemokine requirements for B cell entry to lymph nodes and Peyer's patches. J Exp Med. 2002;196:65-75 pubmed..Here we show that the homing of CXCR4-/- B cells is suppressed in CCL19 (ELC)- and CCL21 (SLC)-deficient paucity of lymph node T cells mice, but not in wild-type mice...
- Sato T, Endoh M, Yoshida H, Yasuo S, Katsuno T, Saito Y, et al. Mammalian Polycomb complexes are required for Peyer's patch development by regulating lymphoid cell proliferation. Gene. 2006;379:166-74 pubmed..We suggest that PcG complexes may act to mediate certain inductive signals maybe through IL-7Ralpha to allow sufficient proliferation of lymphoid inducer cells during PP organogenesis. ..