Skip to main content
PMC home page
Molecular Pathology : MP logoLink to Molecular Pathology : MP
. 1999 Aug;52(4):203–207. doi: 10.1136/mp.52.4.203

Alpha E beta 7.

P J Kilshaw 1
PMCID: PMC395700  PMID: 10694940

Abstract

alpha E beta 7 is a member of the integrin family and is expressed almost exclusively by cells of the T lymphocyte lineage in mucosal tissues. Expression is induced by transforming growth factor beta in the mucosal microenvironment. Genetic elements that control transcription are under investigation and may prove valuable for directing the expression of transgenes in mucosal T cells. The only known ligand for alpha E beta 7 is E-cadherin, which is expressed on epithelial cells. In this article, molecular aspects of ligand recognition by alpha E beta 7 in relation to recent structural data on cadherin domains are reviewed. Expression of alpha E beta 7 is often increased in inflammatory diseases, particularly where T cells infiltrate epithelial tissues. The function of alpha E beta 7 is not yet fully understood, but it is likely to be important in retention of T cells in mucosal tissues and may also have a role in cell signalling and communication between lymphocytes and epithelial surfaces.

Full Text

The Full Text of this article is available as a PDF (163.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alattia J. R., Ames J. B., Porumb T., Tong K. I., Heng Y. M., Ottensmeyer P., Kay C. M., Ikura M. Lateral self-assembly of E-cadherin directed by cooperative calcium binding. FEBS Lett. 1997 Nov 17;417(3):405–408. doi: 10.1016/s0014-5793(97)01333-1. [DOI] [PubMed] [Google Scholar]
  2. Aranda R., Sydora B. C., McAllister P. L., Binder S. W., Yang H. Y., Targan S. R., Kronenberg M. Analysis of intestinal lymphocytes in mouse colitis mediated by transfer of CD4+, CD45RBhigh T cells to SCID recipients. J Immunol. 1997 Apr 1;158(7):3464–3473. [PubMed] [Google Scholar]
  3. Austrup F., Rebstock S., Kilshaw P. J., Hamann A. Transforming growth factor-beta 1-induced expression of the mucosa-related integrin alpha E on lymphocytes is not associated with mucosa-specific homing. Eur J Immunol. 1995 Jun;25(6):1487–1491. doi: 10.1002/eji.1830250602. [DOI] [PubMed] [Google Scholar]
  4. Ben-Ze'ev A., Geiger B. Differential molecular interactions of beta-catenin and plakoglobin in adhesion, signaling and cancer. Curr Opin Cell Biol. 1998 Oct;10(5):629–639. doi: 10.1016/s0955-0674(98)80039-2. [DOI] [PubMed] [Google Scholar]
  5. Bloom S., Simmons D., Jewell D. P. Adhesion molecules intercellular adhesion molecule-1 (ICAM-1), ICAM-3 and B7 are not expressed by epithelium in normal or inflamed colon. Clin Exp Immunol. 1995 Jul;101(1):157–163. doi: 10.1111/j.1365-2249.1995.tb02292.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Calderwood D. A., Tuckwell D. S., Eble J., Kühn K., Humphries M. J. The integrin alpha1 A-domain is a ligand binding site for collagens and laminin. J Biol Chem. 1997 May 9;272(19):12311–12317. doi: 10.1074/jbc.272.19.12311. [DOI] [PubMed] [Google Scholar]
  7. Cepek K. L., Parker C. M., Madara J. L., Brenner M. B. Integrin alpha E beta 7 mediates adhesion of T lymphocytes to epithelial cells. J Immunol. 1993 Apr 15;150(8 Pt 1):3459–3470. [PubMed] [Google Scholar]
  8. Cepek K. L., Shaw S. K., Parker C. M., Russell G. J., Morrow J. S., Rimm D. L., Brenner M. B. Adhesion between epithelial cells and T lymphocytes mediated by E-cadherin and the alpha E beta 7 integrin. Nature. 1994 Nov 10;372(6502):190–193. doi: 10.1038/372190a0. [DOI] [PubMed] [Google Scholar]
  9. Cerf-Bensussan N., Jarry A., Brousse N., Lisowska-Grospierre B., Guy-Grand D., Griscelli C. A monoclonal antibody (HML-1) defining a novel membrane molecule present on human intestinal lymphocytes. Eur J Immunol. 1987 Sep;17(9):1279–1285. doi: 10.1002/eji.1830170910. [DOI] [PubMed] [Google Scholar]
  10. Chitaev N. A., Troyanovsky S. M. Adhesive but not lateral E-cadherin complexes require calcium and catenins for their formation. J Cell Biol. 1998 Aug 10;142(3):837–846. doi: 10.1083/jcb.142.3.837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dickeson S. K., Santoro S. A. Ligand recognition by the I domain-containing integrins. Cell Mol Life Sci. 1998 Jun;54(6):556–566. doi: 10.1007/s000180050184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dietz S. B., Whitaker-Menezes D., Lessin S. R. The role of alpha E beta 7 integrin (CD103) and E-cadherin in epidermotropism in cutaneous T-cell lymphoma. J Cutan Pathol. 1996 Aug;23(4):312–318. doi: 10.1111/j.1600-0560.1996.tb01303.x. [DOI] [PubMed] [Google Scholar]
  13. Elewaut D., Van Damme N., De Keyser F., Baeten D., De Paepe P., Van Vlierberghe H., Mielants H., Cuvelier C., Verbruggen G., Veys E. M. Altered expression of alpha E beta 7 integrin on intra-epithelial and lamina propria lymphocytes in patients with Crohn's disease. Acta Gastroenterol Belg. 1998 Jul-Sep;61(3):288–294. [PubMed] [Google Scholar]
  14. Hadley G. A., Bartlett S. T., Via C. S., Rostapshova E. A., Moainie S. The epithelial cell-specific integrin, CD103 (alpha E integrin), defines a novel subset of alloreactive CD8+ CTL. J Immunol. 1997 Oct 15;159(8):3748–3756. [PubMed] [Google Scholar]
  15. Hamann A., Andrew D. P., Jablonski-Westrich D., Holzmann B., Butcher E. C. Role of alpha 4-integrins in lymphocyte homing to mucosal tissues in vivo. J Immunol. 1994 Apr 1;152(7):3282–3293. [PubMed] [Google Scholar]
  16. Hermiston M. L., Gordon J. I. In vivo analysis of cadherin function in the mouse intestinal epithelium: essential roles in adhesion, maintenance of differentiation, and regulation of programmed cell death. J Cell Biol. 1995 Apr;129(2):489–506. doi: 10.1083/jcb.129.2.489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hermiston M. L., Gordon J. I. Inflammatory bowel disease and adenomas in mice expressing a dominant negative N-cadherin. Science. 1995 Nov 17;270(5239):1203–1207. doi: 10.1126/science.270.5239.1203. [DOI] [PubMed] [Google Scholar]
  18. Higgins J. M., Mandlebrot D. A., Shaw S. K., Russell G. J., Murphy E. A., Chen Y. T., Nelson W. J., Parker C. M., Brenner M. B. Direct and regulated interaction of integrin alphaEbeta7 with E-cadherin. J Cell Biol. 1998 Jan 12;140(1):197–210. doi: 10.1083/jcb.140.1.197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Holness C. L., Simmons D. L. Structural motifs for recognition and adhesion in members of the immunoglobulin superfamily. J Cell Sci. 1994 Aug;107(Pt 8):2065–2070. doi: 10.1242/jcs.107.8.2065. [DOI] [PubMed] [Google Scholar]
  20. Jankowski J. A., Bedford F. K., Boulton R. A., Cruickshank N., Hall C., Elder J., Allan R., Forbes A., Kim Y. S., Wright N. A. Alterations in classical cadherins associated with progression in ulcerative and Crohn's colitis. Lab Invest. 1998 Sep;78(9):1155–1167. [PubMed] [Google Scholar]
  21. Kamata T., Takada Y. Direct binding of collagen to the I domain of integrin alpha 2 beta 1 (VLA-2, CD49b/CD29) in a divalent cation-independent manner. J Biol Chem. 1994 Oct 21;269(42):26006–26010. [PubMed] [Google Scholar]
  22. Karecla P. I., Bowden S. J., Green S. J., Kilshaw P. J. Recognition of E-cadherin on epithelial cells by the mucosal T cell integrin alpha M290 beta 7 (alpha E beta 7). Eur J Immunol. 1995 Mar;25(3):852–856. doi: 10.1002/eji.1830250333. [DOI] [PubMed] [Google Scholar]
  23. Karecla P. I., Green S. J., Bowden S. J., Coadwell J., Kilshaw P. J. Identification of a binding site for integrin alphaEbeta7 in the N-terminal domain of E-cadherin. J Biol Chem. 1996 Nov 29;271(48):30909–30915. doi: 10.1074/jbc.271.48.30909. [DOI] [PubMed] [Google Scholar]
  24. Kilshaw P. J., Baker K. C. A unique surface antigen on intraepithelial lymphocytes in the mouse. Immunol Lett. 1988 Jun;18(2):149–154. doi: 10.1016/0165-2478(88)90056-9. [DOI] [PubMed] [Google Scholar]
  25. Kilshaw P. J. Expression of the mucosal T cell integrin alpha M290 beta 7 by a major subpopulation of dendritic cells in mice. Eur J Immunol. 1993 Dec;23(12):3365–3368. doi: 10.1002/eji.1830231246. [DOI] [PubMed] [Google Scholar]
  26. Kilshaw P. J., Murant S. J. A new surface antigen on intraepithelial lymphocytes in the intestine. Eur J Immunol. 1990 Oct;20(10):2201–2207. doi: 10.1002/eji.1830201008. [DOI] [PubMed] [Google Scholar]
  27. Kilshaw P. J., Murant S. J. Expression and regulation of beta 7(beta p) integrins on mouse lymphocytes: relevance to the mucosal immune system. Eur J Immunol. 1991 Oct;21(10):2591–2597. doi: 10.1002/eji.1830211041. [DOI] [PubMed] [Google Scholar]
  28. Koch A. W., Pokutta S., Lustig A., Engel J. Calcium binding and homoassociation of E-cadherin domains. Biochemistry. 1997 Jun 24;36(25):7697–7705. doi: 10.1021/bi9705624. [DOI] [PubMed] [Google Scholar]
  29. Kroneld U., Jonsson R., Carlsten H., Bremell T., Johannessen A. C., Tarkowski A. Expression of the mucosal lymphocyte integrin alphaEbeta7 and its ligand E-cadherin in salivary glands of patients with Sjögren's syndrome. Scand J Rheumatol. 1998;27(3):215–218. doi: 10.1080/030097498440831. [DOI] [PubMed] [Google Scholar]
  30. Lim S. P., Leung E., Krissansen G. W. The beta7 integrin gene (Itgb-7) promoter is responsive to TGF-beta1: defining control regions. Immunogenetics. 1998 Aug;48(3):184–195. doi: 10.1007/s002510050422. [DOI] [PubMed] [Google Scholar]
  31. Lúdvíksson B. R., Strober W., Nishikomori R., Hasan S. K., Ehrhardt R. O. Administration of mAb against alpha E beta 7 prevents and ameliorates immunization-induced colitis in IL-2-/- mice. J Immunol. 1999 Apr 15;162(8):4975–4982. [PubMed] [Google Scholar]
  32. Marrs J. A., Nelson W. J. Cadherin cell adhesion molecules in differentiation and embryogenesis. Int Rev Cytol. 1996;165:159–205. doi: 10.1016/s0074-7696(08)62222-6. [DOI] [PubMed] [Google Scholar]
  33. Nagar B., Overduin M., Ikura M., Rini J. M. Structural basis of calcium-induced E-cadherin rigidification and dimerization. Nature. 1996 Mar 28;380(6572):360–364. doi: 10.1038/380360a0. [DOI] [PubMed] [Google Scholar]
  34. Overduin M., Harvey T. S., Bagby S., Tong K. I., Yau P., Takeichi M., Ikura M. Solution structure of the epithelial cadherin domain responsible for selective cell adhesion. Science. 1995 Jan 20;267(5196):386–389. doi: 10.1126/science.7824937. [DOI] [PubMed] [Google Scholar]
  35. Ozawa M., Kemler R. The membrane-proximal region of the E-cadherin cytoplasmic domain prevents dimerization and negatively regulates adhesion activity. J Cell Biol. 1998 Sep 21;142(6):1605–1613. doi: 10.1083/jcb.142.6.1605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Pang M., Abe T., Fujihara T., Mori S., Tsuzaka K., Amano K., Koide J., Takeuchi T. Up-regulation of alphaEbeta7, a novel integrin adhesion molecule, on T cells from systemic lupus erythematosus patients with specific epithelial involvement. Arthritis Rheum. 1998 Aug;41(8):1456–1463. doi: 10.1002/1529-0131(199808)41:8<1456::AID-ART16>3.0.CO;2-0. [DOI] [PubMed] [Google Scholar]
  37. Parkos C. A., Colgan S. P., Diamond M. S., Nusrat A., Liang T. W., Springer T. A., Madara J. L. Expression and polarization of intercellular adhesion molecule-1 on human intestinal epithelia: consequences for CD11b/CD18-mediated interactions with neutrophils. Mol Med. 1996 Jul;2(4):489–505. [PMC free article] [PubMed] [Google Scholar]
  38. Randi A. M., Hogg N. I domain of beta 2 integrin lymphocyte function-associated antigen-1 contains a binding site for ligand intercellular adhesion molecule-1. J Biol Chem. 1994 Apr 29;269(17):12395–12398. [PubMed] [Google Scholar]
  39. Rietzler M., Bittner M., Kolanus W., Schuster A., Holzmann B. The human WD repeat protein WAIT-1 specifically interacts with the cytoplasmic tails of beta7-integrins. J Biol Chem. 1998 Oct 16;273(42):27459–27466. doi: 10.1074/jbc.273.42.27459. [DOI] [PubMed] [Google Scholar]
  40. Rihs S., Walker C., Virchow J. C., Jr, Boer C., Kroegel C., Giri S. N., Braun R. K. Differential expression of alpha E beta 7 integrins on bronchoalveolar lavage T lymphocyte subsets: regulation by alpha 4 beta 1-integrin crosslinking and TGF-beta. Am J Respir Cell Mol Biol. 1996 Nov;15(5):600–610. doi: 10.1165/ajrcmb.15.5.8918367. [DOI] [PubMed] [Google Scholar]
  41. Roberts A. I., O'Connell S. M., Biancone L., Brolin R. E., Ebert E. C. Spontaneous cytotoxicity of intestinal intraepithelial lymphocytes: clues to the mechanism. Clin Exp Immunol. 1993 Dec;94(3):527–532. doi: 10.1111/j.1365-2249.1993.tb08229.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Roberts K., Kilshaw P. J. The mucosal T cell integrin alpha M290 beta 7 recognizes a ligand on mucosal epithelial cell lines. Eur J Immunol. 1993 Jul;23(7):1630–1635. doi: 10.1002/eji.1830230735. [DOI] [PubMed] [Google Scholar]
  43. Rubio Félix S., Aznar Munoz R., Martín Algora I., Egido Murciano M., Ferrero Cáncer M., Mairal Claver P., Rezusta López A. Bacteriemia en el anciano: factores asociados y pronósticos. Rev Clin Esp. 1998 Jan;198(1):7–10. [PubMed] [Google Scholar]
  44. Sarnacki S., Bègue B., Buc H., Le Deist F., Cerf-Bensussan N. Enhancement of CD3-induced activation of human intestinal intraepithelial lymphocytes by stimulation of the beta 7-containing integrin defined by HML-1 monoclonal antibody. Eur J Immunol. 1992 Nov;22(11):2887–2892. doi: 10.1002/eji.1830221120. [DOI] [PubMed] [Google Scholar]
  45. Shapiro L., Fannon A. M., Kwong P. D., Thompson A., Lehmann M. S., Grübel G., Legrand J. F., Als-Nielsen J., Colman D. R., Hendrickson W. A. Structural basis of cell-cell adhesion by cadherins. Nature. 1995 Mar 23;374(6520):327–337. doi: 10.1038/374327a0. [DOI] [PubMed] [Google Scholar]
  46. Shaw S. K., Cepek K. L., Murphy E. A., Russell G. J., Brenner M. B., Parker C. M. Molecular cloning of the human mucosal lymphocyte integrin alpha E subunit. Unusual structure and restricted RNA distribution. J Biol Chem. 1994 Feb 25;269(8):6016–6025. [PubMed] [Google Scholar]
  47. Shi Y., Wang Y. F., Jayaraman L., Yang H., Massagué J., Pavletich N. P. Crystal structure of a Smad MH1 domain bound to DNA: insights on DNA binding in TGF-beta signaling. Cell. 1998 Sep 4;94(5):585–594. doi: 10.1016/s0092-8674(00)81600-1. [DOI] [PubMed] [Google Scholar]
  48. Smith T. J., Ducharme L. A., Shaw S. K., Parker C. M., Brenner M. B., Kilshaw P. J., Weis J. H. Murine M290 integrin expression modulated by mast cell activation. Immunity. 1994 Aug;1(5):393–403. doi: 10.1016/1074-7613(94)90070-1. [DOI] [PubMed] [Google Scholar]
  49. Stewart M., Hogg N. Regulation of leukocyte integrin function: affinity vs. avidity. J Cell Biochem. 1996 Jun 15;61(4):554–561. doi: 10.1002/(sici)1097-4644(19960616)61:4<554::aid-jcb8>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
  50. Tlsty T. D. Cell-adhesion-dependent influences on genomic instability and carcinogenesis. Curr Opin Cell Biol. 1998 Oct;10(5):647–653. doi: 10.1016/s0955-0674(98)80041-0. [DOI] [PubMed] [Google Scholar]
  51. Tomschy A., Fauser C., Landwehr R., Engel J. Homophilic adhesion of E-cadherin occurs by a co-operative two-step interaction of N-terminal domains. EMBO J. 1996 Jul 15;15(14):3507–3514. [PMC free article] [PubMed] [Google Scholar]
  52. Trollmo C., Nilsson I. M., Sollerman C., Tarkowski A. Expression of the mucosal lymphocyte integrin alpha E beta 7 and its ligand E-cadherin in the synovium of patients with rheumatoid arthritis. Scand J Immunol. 1996 Sep;44(3):293–298. [PubMed] [Google Scholar]
  53. Ueda T., Rieu P., Brayer J., Arnaout M. A. Identification of the complement iC3b binding site in the beta 2 integrin CR3 (CD11b/CD18). Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10680–10684. doi: 10.1073/pnas.91.22.10680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Viney J. L., Jones S., Chiu H. H., Lagrimas B., Renz M. E., Presta L. G., Jackson D., Hillan K. J., Lew S., Fong S. Mucosal addressin cell adhesion molecule-1: a structural and functional analysis demarcates the integrin binding motif. J Immunol. 1996 Sep 15;157(6):2488–2497. [PubMed] [Google Scholar]
  55. Yap A. S., Brieher W. M., Gumbiner B. M. Molecular and functional analysis of cadherin-based adherens junctions. Annu Rev Cell Dev Biol. 1997;13:119–146. doi: 10.1146/annurev.cellbio.13.1.119. [DOI] [PubMed] [Google Scholar]
  56. Yap A. S., Niessen C. M., Gumbiner B. M. The juxtamembrane region of the cadherin cytoplasmic tail supports lateral clustering, adhesive strengthening, and interaction with p120ctn. J Cell Biol. 1998 May 4;141(3):779–789. doi: 10.1083/jcb.141.3.779. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Molecular Pathology are provided here courtesy of BMJ Publishing Group

RESOURCES