lymphocyte homing receptors


Summary: Cell surface glycoproteins on lymphocytes and other leukocytes that mediate adhesion to specialized blood vessels called high endothelial venules. Several different classes of lymphocyte homing receptors have been identified, and they appear to target different surface molecules (addressins) on high endothelial venules in different tissues. The adhesion plays a crucial role in the trafficking of lymphocytes.

Top Publications

  1. Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature. 1999;401:708-12 pubmed
  2. Sackstein R. The lymphocyte homing receptors: gatekeepers of the multistep paradigm. Curr Opin Hematol. 2005;12:444-50 pubmed
    ..The cross-talk among the homing receptors and integrins opens a new 'avenue' to lymphocyte migration, suggesting that homing receptors may be sufficient alone, in some cases, to perform the function the name implies. ..
  3. Mora J, Bono M, Manjunath N, Weninger W, Cavanagh L, Rosemblatt M, et al. Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells. Nature. 2003;424:88-93 pubmed
    ..These findings establish that Peyer's patch dendritic cells imprint gut-homing specificity on T cells, and thus license effector/memory cells to access anatomical sites most likely to contain their cognate antigen. ..
  4. 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
    ..These findings establish the principal chemokine and chemokine receptor requirements for B cell entry to lymph nodes and Peyer's patches. ..
  5. Homey B, Alenius H, Muller A, Soto H, Bowman E, Yuan W, et al. CCL27-CCR10 interactions regulate T cell-mediated skin inflammation. Nat Med. 2002;8:157-65 pubmed
    ..Together, these findings indicate that CCL27-CCR10 interactions have a pivotal role in T cell-mediated skin inflammation. ..
  6. Zabel B, Agace W, Campbell J, Heath H, Parent D, Roberts A, et al. Human G protein-coupled receptor GPR-9-6/CC chemokine receptor 9 is selectively expressed on intestinal homing T lymphocytes, mucosal lymphocytes, and thymocytes and is required for thymus-expressed chemokine-mediated chemotaxis. J Exp Med. 1999;190:1241-56 pubmed
    ..The selective expression of TECK and GPR-9-6 in thymus and small intestine implies a dual role for GPR-9-6/CCR-9, both in T cell development and the mucosal immune response. ..
  7. Seoh J, Park H, Chung W, Kim S, Hahn M, Kim K, et al. Cell cycling status of human cord blood CD34+ cells during ex vivo expansion is related to the level of very late antigen expression. J Korean Med Sci. 2001;16:20-4 pubmed
    ..001). Furthermore, the fraction of cells in S/G2/M phase increased as the expression of VLA-4 became higher. These results suggest that cord blood CD34+ cells expressing high levels of VLA-4 have more proliferative activities. ..
  8. Schaerli P, Willimann K, Lang A, Lipp M, Loetscher P, Moser B. CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Exp Med. 2000;192:1553-62 pubmed
    ..These properties portray CXCR5(+) T cells as a distinct memory T cell subset with B cell helper function, designated here as follicular B helper T cells (T(FH)). ..
  9. Yakubenko V, Lobb R, Plow E, Ugarova T. Differential induction of gelatinase B (MMP-9) and gelatinase A (MMP-2) in T lymphocytes upon alpha(4)beta(1)-mediated adhesion to VCAM-1 and the CS-1 peptide of fibronectin. Exp Cell Res. 2000;260:73-84 pubmed

More Information


  1. Goodarzi K, Goodarzi M, Tager A, Luster A, von Andrian U. Leukotriene B4 and BLT1 control cytotoxic effector T cell recruitment to inflamed tissues. Nat Immunol. 2003;4:965-73 pubmed
    ..These results identify LTB4-BLT1 as a potent nonchemokine pathway for cytotoxic effector cell traffic. ..
  2. Issekutz A, Issekutz T. The role of E-selectin, P-selectin, and very late activation antigen-4 in T lymphocyte migration to dermal inflammation. J Immunol. 2002;168:1934-9 pubmed
  3. Ramirez M, Segovia J, Benet I, Arbona C, Guenechea G, Blaya C, et al. Ex vivo expansion of umbilical cord blood (UCB) CD34(+) cells alters the expression and function of alpha 4 beta 1 and alpha 5 beta 1 integrins. Br J Haematol. 2001;115:213-21 pubmed
    ..However, in vivo, these effects induced an almost complete abrogation of the homing and repopulating ability of CD34(+) UCB cells. ..
  4. Yeh J, Hiraoka N, Petryniak B, Nakayama J, Ellies L, Rabuka D, et al. Novel sulfated lymphocyte homing receptors and their control by a Core1 extension beta 1,3-N-acetylglucosaminyltransferase. Cell. 2001;105:957-69 pubmed
    ..These results identify Core1-beta 3GlcNAcT and its cognate extended core1 O-glycans as essential participants in the expression of the MECA-79-positive, HEV-specific L-selectin ligands required for lymphocyte homing. ..
  5. Arroyo A, Taverna D, Whittaker C, Strauch U, Bader B, Rayburn H, et al. In vivo roles of integrins during leukocyte development and traffic: insights from the analysis of mice chimeric for alpha 5, alpha v, and alpha 4 integrins. J Immunol. 2000;165:4667-75 pubmed
    ..These results show that integrins play distinct roles during in vivo leukocyte development and traffic. ..
  6. Connor E, Eppihimer M, Morise Z, Granger D, Grisham M. Expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in acute and chronic inflammation. J Leukoc Biol. 1999;65:349-55 pubmed
  7. de Château M, Chen S, Salas A, Springer T. Kinetic and mechanical basis of rolling through an integrin and novel Ca2+-dependent rolling and Mg2+-dependent firm adhesion modalities for the alpha 4 beta 7-MAdCAM-1 interaction. Biochemistry. 2001;40:13972-9 pubmed
  8. Iellem A, Colantonio L, D Ambrosio D. Skin-versus gut-skewed homing receptor expression and intrinsic CCR4 expression on human peripheral blood CD4+CD25+ suppressor T cells. Eur J Immunol. 2003;33:1488-96 pubmed
    ..These observations indicate that the increased expression of CCR4, which is proposed to guide CD25(+) Ts cells to DC, is an intrinsic feature of CD25(+) Ts cells. ..
  9. Picker L, Nakache M, Butcher E. Monoclonal antibodies to human lymphocyte homing receptors define a novel class of adhesion molecules on diverse cell types. J Cell Biol. 1989;109:927-37 pubmed
    ..To ask whether these non-lymphoid molecules might also be functionally homologous to lymphocyte homing receptors, we assessed their ability to interact with purified MAd using fluorescence energy transfer techniques...
  10. Lund Johansen F, Terstappen L. Differential surface expression of cell adhesion molecules during granulocyte maturation. J Leukoc Biol. 1993;54:47-55 pubmed
    ..In contrast, sLex and CD67 were specifically expressed by myeloid cells and could be specifically important for compartmentalization of distinct phases of granulocyte maturation. ..
  11. Picker L, Terstappen L, Rott L, Streeter P, Stein H, Butcher E. Differential expression of homing-associated adhesion molecules by T cell subsets in man. J Immunol. 1990;145:3247-55 pubmed
  12. Jalkanen S, Aho R, Kallajoki M, Ekfors T, Nortamo P, Gahmberg C, et al. Lymphocyte homing receptors and adhesion molecules in intravascular malignant lymphomatosis. Int J Cancer. 1989;44:777-82 pubmed
  13. Yednock T, Cannon C, Vandevert C, Goldbach E, Shaw G, Ellis D, et al. Alpha 4 beta 1 integrin-dependent cell adhesion is regulated by a low affinity receptor pool that is conformationally responsive to ligand. J Biol Chem. 1995;270:28740-50 pubmed
    ..These studies provide insight into how cells maintain different constitutive levels of alpha 4 beta 1 integrin activity, and how the activity of beta 1 integrin can be modulated by activators of cell adhesion. ..
  14. Pujades C, Teixido J, Bazzoni G, Hemler M. Integrin alpha 4 cysteines 278 and 717 modulate VLA-4 ligand binding and also contribute to alpha 4/180 formation. Biochem J. 1996;313 ( Pt 3):899-908 pubmed
    ..Biol. Chem. 268, 7028-2035] also requires Cys 278 and Cys 717, divalent cations and reduced cysteines. thus alpha 4/180 appears to be more functionally relevant than alpha 4/150. ..
  15. Picarella D, Hurlbut P, Rottman J, Shi X, Butcher E, Ringler D. Monoclonal antibodies specific for beta 7 integrin and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) reduce inflammation in the colon of scid mice reconstituted with CD45RBhigh CD4+ T cells. J Immunol. 1997;158:2099-106 pubmed
  16. Fong S, Jones S, Renz M, Chiu H, Ryan A, Presta L, et al. Mucosal addressin cell adhesion molecule-1 (MAdCAM-1). Its binding motif for alpha 4 beta 7 and role in experimental colitis. Immunol Res. 1997;16:299-311 pubmed
  17. Bonecchi R, Bianchi G, Bordignon P, D Ambrosio D, Lang R, Borsatti A, et al. Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J Exp Med. 1998;187:129-34 pubmed
    ..It may also determine different susceptibility of Th1s and Th2s to human immunodeficiency virus strains using different fusion coreceptors. ..
  18. Berg E, McEvoy L, Berlin C, Bargatze R, Butcher E. L-selectin-mediated lymphocyte rolling on MAdCAM-1. Nature. 1993;366:695-8 pubmed
    ..7), and may be uniquely adapted to support both selectin-mediated lymphocyte rolling and integrin-mediated adhesion and arrest in vivo. ..
  19. Dogan A, Du M, Koulis A, Briskin M, Isaacson P. Expression of lymphocyte homing receptors and vascular addressins in low-grade gastric B-cell lymphomas of mucosa-associated lymphoid tissue. Am J Pathol. 1997;151:1361-9 pubmed
    ..These findings suggest expression of lymphocyte homing receptors by B cells and vascular addressins by mucosal venules are similar in normal MALT and MALT lymphomas, ..
  20. Arbones M, Ord D, Ley K, Ratech H, Maynard Curry C, Otten G, et al. Lymphocyte homing and leukocyte rolling and migration are impaired in L-selectin-deficient mice. Immunity. 1994;1:247-60 pubmed
    ..Thus, L-selectin plays an essential role in leukocyte homing to lymphoid tissues and sites of inflammation. ..
  21. Briskin M, Winsor Hines D, Shyjan A, Cochran N, Bloom S, Wilson J, et al. Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in intestinal tract and associated lymphoid tissue. Am J Pathol. 1997;151:97-110 pubmed
    ..As such, the pathway defined by MAdCAM-1/alpha 4 beta 7 may be a relevant tissue-specific therapeutic target for the modulation of inflammatory bowel disease activity. ..
  22. Kwee L, Baldwin H, Shen H, Stewart C, Buck C, Buck C, et al. Defective development of the embryonic and extraembryonic circulatory systems in vascular cell adhesion molecule (VCAM-1) deficient mice. Development. 1995;121:489-503 pubmed
    ..These data suggest important roles for VCAM-1 and alpha 4 in the development of the placenta and the heart. ..
  23. Yang J, Rayburn H, Hynes R. Cell adhesion events mediated by alpha 4 integrins are essential in placental and cardiac development. Development. 1995;121:549-60 pubmed
    ..These results raise the possibility of abortifacients targeting alpha 4 integrins, and raise serious questions about potential side effects of drugs currently being designed to block alpha 4 integrin functions in inflammation. ..
  24. Kirby A, Lodi G, Olsen I, Porter S. Immunohistochemical and serological comparison of idiopathic and hepatitis C virus-associated forms of oral lichen planus. Eur J Oral Sci. 1998;106:853-62 pubmed
    ..These findings show that there are some differences in the lesional and systemic immune reactivities of the two types of oral lichen planus which may be related to possibly distinct pathogenic mechanisms. ..
  25. Mebius R, Schadee Eestermans I, Weissman I. MAdCAM-1 dependent colonization of developing lymph nodes involves a unique subset of CD4+CD3- hematolymphoid cells. Cell Adhes Commun. 1998;6:97-103 pubmed
    ..In view of the necessity of lymphotoxin in lymphoid organ development, it is thought that the novel subset of CD4+CD3- LTbeta+ fetal cells is instrumental in the development of lymphoid tissue architecture. ..
  26. Annels N, Willemze A, van der Velden V, Faaij C, van Wering E, Sie Go D, et al. Possible link between unique chemokine and homing receptor expression at diagnosis and relapse location in a patient with childhood T-ALL. Blood. 2004;103:2806-8 pubmed
    ..These findings suggest that the original expression of CCR9 and CD103 on the leukemic cells contributed to the relapse location in the gut of this patient. ..
  27. Bhatia R, Williams A, Munthe H. Contact with fibronectin enhances preservation of normal but not chronic myelogenous leukemia primitive hematopoietic progenitors. Exp Hematol. 2002;30:324-32 pubmed
    ..We conclude that beta1 integrin-FN interactions enhance normal primitive progenitor preservation with or without cell division, and that these mechanisms are impaired in CML primitive progenitors. ..
  28. Iwata M, Hirakiyama A, Eshima Y, Kagechika H, Kato C, Song S. Retinoic acid imprints gut-homing specificity on T cells. Immunity. 2004;21:527-38 pubmed
    ..These findings revealed a novel role for retinoic acid in the imprinting of gut-homing specificity on T cells. ..
  29. Harp J, Waters T, Goff J. Adhesion molecule and homing receptor expression on blood and milk polymorphonuclear leukocytes during the periparturient period of dairy cattle. Vet Immunol Immunopathol. 2005;104:99-103 pubmed
    ..05) greater than in blood at all time points. The MFI of CD11a on milk PMN was consistently higher than that of blood PMN throughout the study period and significantly (P<0.05) higher at days 4, 10 and 18 after calving. ..
  30. Ricard I, Payet M, Dupuis G. VCAM-1 is internalized by a clathrin-related pathway in human endothelial cells but its alpha 4 beta 1 integrin counter-receptor remains associated with the plasma membrane in human T lymphocytes. Eur J Immunol. 1998;28:1708-18 pubmed
    ..The persistent cell surface expression of alpha 4 beta 1 integrin would allow the migrating T cells to interact with and receive signal(s) from its fibronectin ligand of the extracellular matrix. ..
  31. Papayannopoulou T, Priestley G, Nakamoto B, Zafiropoulos V, Scott L. Molecular pathways in bone marrow homing: dominant role of alpha(4)beta(1) over beta(2)-integrins and selectins. Blood. 2001;98:2403-11 pubmed
  32. Weekes C, Kuszynski C, Sharp J. VLA-4 mediated adhesion to bone marrow stromal cells confers chemoresistance to adherent lymphoma cells. Leuk Lymphoma. 2001;40:631-45 pubmed
    ..These data demonstrated that viable bone marrow stromal cells possessed the ability to actively inhibit the apoptotic pathways of intimately adherent lymphoma cells and this potentially contributes to their survival during chemotherapy. ..
  33. Johnston B, Chee A, Issekutz T, Ugarova T, Fox Robichaud A, Hickey M, et al. Alpha 4 integrin-dependent leukocyte recruitment does not require VCAM-1 in a chronic model of inflammation. J Immunol. 2000;164:3337-44 pubmed
    ..These findings provide the first evidence that alpha 4 beta 1 integrin-dependent leukocyte rolling and adhesion can occur in vivo via a mechanism other than VCAM-1. ..
  34. Furuhashi T, Yamaguchi Y, Wang F, Uchino S, Okabe K, Ohshiro H, et al. Hepatic CCR7lowCD62LlowCD45RClow allograft dendritic cells migrate to the splenic red pulp in immunologically unresponsive rats. J Surg Res. 2005;124:29-37 pubmed
    ..In conclusion, differential splenic migration of CCR5lowCCR7lowCD62Llow CD45RClow DC expressing Th2-type cytokines is associated with immunological unresponsiveness to rat hepatic allografts. ..
  35. Schutyser E, Richmond A, Van Damme J. Involvement of CC chemokine ligand 18 (CCL18) in normal and pathological processes. J Leukoc Biol. 2005;78:14-26 pubmed
    ..The lack of a rodent counterpart for human CCL18 sets all hope on primate animal models to further elucidate the importance of CCL18 in vivo. This review will address these different aspects in more detail. ..
  36. Halary F, Pitard V, Dlubek D, Krzysiek R, de la Salle H, Merville P, et al. Shared reactivity of V{delta}2(neg) {gamma}{delta} T cells against cytomegalovirus-infected cells and tumor intestinal epithelial cells. J Exp Med. 2005;201:1567-78 pubmed
  37. Shibahara T, Miyazaki K, Sato D, Matsui H, Yanaka A, Nakahara A, et al. Alteration of intestinal epithelial function by intraepithelial lymphocyte homing. J Gastroenterol. 2005;40:878-86 pubmed
    ..Because such alterations may increase epithelial permeability to luminal antigens or accelerate the migration of other inflammatory cells, our results suggest that IEL have a critical role in mucosal immunity. ..
  38. Gurses N, Thorup A, Reibel J, Carter W, Holmstrup P. Expression of VLA-integrins and their related basement membrane ligands in gingiva from patients of various periodontitis categories. J Clin Periodontol. 1999;26:217-24 pubmed
    ..Clarification of expressions of integrins and their ligands in relation to known clinical disease susceptibility factors may provide information on the onset and progression mechanisms of periodontal disease destruction. ..
  39. Yong K, Fahey A, Pahal G, Linch D, Pizzey A, Thomas N, et al. Fetal haemopoietic cells display enhanced migration across endothelium. Br J Haematol. 2002;116:392-400 pubmed
    ..The superior migratory activity of fetal haemopoietic cells may underlie a more efficient homing ability, in keeping with their physiological role. ..
  40. Sydora B, Wagner N, Lohler J, Yakoub G, Kronenberg M, Muller W, et al. beta7 Integrin expression is not required for the localization of T cells to the intestine and colitis pathogenesis. Clin Exp Immunol. 2002;129:35-42 pubmed
    ..These results show that beta7 integrin expression is not absolutely required for T cell localization to the intestine and colitis pathogenesis. ..
  41. Ladi E, Yin X, Chtanova T, Robey E. Thymic microenvironments for T cell differentiation and selection. Nat Immunol. 2006;7:338-43 pubmed
    ..In addition, we discuss the diverse developmental signals provided by these microenvironments that contribute to the generation of divergent T cell lineages. ..
  42. Nishimura T, Koike R, Miyasaka M. Mammary glands of Aly mice: developmental changes and lactation-related expression of specific proteins, alpha-casein, GLyCAM-1 and MAdCAM-1. Am J Reprod Immunol. 2000;43:351-8 pubmed
    ..Our results demonstrated marked changes in the structure of the mammary glands of aly/aly mice. The expression of lactation-related proteins was detected during development, pregnancy, and lactation in both aly/aly and aly/+ mice. ..
  43. Fisher A, DePuy E, Jayaraj A, Raab C, Braun M, Ellis Hutchings M, et al. LC/MS/MS plasma assay for the peptidomimetic VLA4 antagonist I and its major active metabolite II: for treatment of asthma by inhalation. J Pharm Biomed Anal. 2002;27:57-71 pubmed
    ..0-101.7% and 1.39-9.28% CV, respectively. Extraction recovery averaged 63.7% for I and 64.9% for II. This general assay methodology may be applied to assay small acidic peptides and peptidomimetics from biological fluids by LC/MS/MS. ..
  44. Shang X, Lang B, Issekutz A. Adhesion molecule mechanisms mediating monocyte migration through synovial fibroblast and endothelium barriers: role for CD11/CD18, very late antigen-4 (CD49d/CD29), very late antigen-5 (CD49e/CD29), and vascular cell adhesion molecule-1 (CD106). J Immunol. 1998;160:467-74 pubmed
    ..In addition to VCAM-1, other ligand(s) on HSF are also involved in the VLA-4-mediated migration. ..
  45. Steidl U, Steidl C, Ebralidze A, Chapuy B, Han H, Will B, et al. A distal single nucleotide polymorphism alters long-range regulation of the PU.1 gene in acute myeloid leukemia. J Clin Invest. 2007;117:2611-20 pubmed
    ..Thus we have identified a SNP within a distal enhancer that is associated with a subtype of leukemia and exerts a deleterious effect through remote transcriptional dysregulation in specific progenitor subtypes. ..
  46. Kang S, Lim H, Andrisani O, Broxmeyer H, Kim C. Vitamin A metabolites induce gut-homing FoxP3+ regulatory T cells. J Immunol. 2007;179:3724-33 pubmed
    ..Taken together, these results identify retinoids as positive regulatory factors for generation of gut-homing FoxP3+ T cells...
  47. Agger R, Petersen M, Petersen C, Hansen S, Stødkilde Jørgensen H, Skands U, et al. T cell homing to tumors detected by 3D-coordinated positron emission tomography and magnetic resonance imaging. J Immunother. 2007;30:29-39 pubmed
    ..Accumulation of 124I was significantly higher in B16-OVA than in B16 tumors not expressing the OVA antigen. ..
  48. Kantele J, Savilahti E, Westerholm Ormio M, Pakkanen S, Arvilommi H, Reunala T, et al. Decreased numbers of circulating plasmablasts and differences in IgA1-plasmablast homing to skin in coeliac disease and dermatitis herpetiformis. Clin Exp Immunol. 2009;156:535-41 pubmed publisher
    ..Differential IgA1-plasmablast homing could be associated with the development of skin rash with IgA1-deposits in DH but not in CD. ..
  49. Brown K. Lymphocyte trafficking, survival and proliferation. Trends Immunol. 2002;23:275-7 pubmed
  50. Takeuchi T, Abe T. 2. Role of adhesion molecules in vasculitis syndrome. Intern Med. 2002;41:41-4 pubmed
  51. Li H, Jiang X, Goodman M. Synthesis, conformational analysis and biological activities of lanthionine analogs of a cell adhesion modulator. J Pept Sci. 2001;7:82-91 pubmed
    ..Both molecules adopt similar topological arrangements in their conformations, while some important differences remain in the sulfur bridge region, which may cause the difference in potency. ..
  52. Jaakkola K, Jalkanen S, Kaunismäki K, Vänttinen E, Saukko P, Alanen K, et al. Vascular adhesion protein-1, intercellular adhesion molecule-1 and P-selectin mediate leukocyte binding to ischemic heart in humans. J Am Coll Cardiol. 2000;36:122-9 pubmed
    ..Human P-selectin, ICAM-1 and VAP-1 appear to be the most promising targets when antiadhesive interventions preventing leukocyte-mediated tissue destruction after myocardial ischemia are planned. ..
  53. Sallusto F, Kremmer E, Palermo B, Hoy A, Ponath P, Qin S, et al. Switch in chemokine receptor expression upon TCR stimulation reveals novel homing potential for recently activated T cells. Eur J Immunol. 1999;29:2037-45 pubmed
    ..As a result, T cells that are activated in tissues may either recirculate to draining lymph nodes or migrate to nearby sites of organized ectopic lymphoid tissues. ..