ITGAE explained

Integrin, alpha E (ITGAE) also known as CD103 (cluster of differentiation 103) is an integrin protein that in human is encoded by the ITGAE gene.^{[1] [2]} CD103 binds integrin beta 7 (β7– ITGB7) to form the complete heterodimeric integrin molecule αEβ7, which has no distinct name. The αEβ7 complex is often referred to as "CD103" though this strictly refers only to the αE chain. Note that the β7 subunit can bind with other integrin α chains, such as α4 (CD49d).

Tissue distribution

CD103 is expressed widely on intraepithelial lymphocyte (IEL) T cells (both αβ T cells and γδ T cells) and on some peripheral regulatory T cells (Tregs).^[3] It has also been reported on lamina propria T cells.^[4] A subset of dendritic cells in the gut mucosa and mesenteric lymph nodes, known as CD103 dendritic cells, also expresses this marker.^[5]

It is useful in identifying hairy cell leukemia which is positive for this marker in contrast to most other hematologic malignancies which are negative for CD103 except for hairy cell leukemia variant, a fraction of splenic marginal zone lymphomas, and enteropathy-associated T cell lymphoma.^[6]

Function

The chief ligand for αEβ7 is E-cadherin, a cellular adhesion molecule (CAM) found on epithelial cells.^[7] It is probably important for T cell homing to the intestinal sites^[8] and thymocyte contacts with thymic reticuloepithelial cells.^[9]

Tregs are important for decreasing the immune response and appear to play a crucial role in the prevention of autoimmune diseases. Tregs are defined as CD4⁺/CD25⁺/Foxp3⁺ cells.^[10] Some CD4⁺/FoxP3⁻ cells also express CD103 and have been attributed regulatory activity. It is unclear whether the presence of CD103 on Treg cells represents a specialized feature for Treg, or Treg differentiation of IEL T cells.

See also

• Cluster of differentiation
• Tissue-resident memory T cell

Further reading

• Davila S, Froeling FE, Tan A, Bonnard C, Boland GJ, Snippe H, Hibberd ML, Seielstad M . New genetic associations detected in a host response study to hepatitis B vaccine . Genes and Immunity . 11 . 3 . 232–238 . April 2010 . 20237496 . 10.1038/gene.2010.1 . free .
• Tilburgs T, Scherjon SA, Roelen DL, Claas FH . Decidual CD8+CD28- T cells express CD103 but not perforin . Human Immunology . 70 . 2 . 96–100 . February 2009 . 19150377 . 10.1016/j.humimm.2008.12.006 .
• Schlickum S, Sennefelder H, Friedrich M, Harms G, Lohse MJ, Kilshaw P, Schön MP . Integrin alpha E(CD103)beta 7 influences cellular shape and motility in a ligand-dependent fashion . Blood . 112 . 3 . 619–625 . August 2008 . 18492951 . 10.1182/blood-2008-01-134833 . free .
• Rose JE, Behm FM, Drgon T, Johnson C, Uhl GR . Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score . Molecular Medicine . 16 . 7–8 . 247–253 . 2010 . 20379614 . 2896464 . 10.2119/molmed.2009.00159 .
• Liu YH, Chen RH, Chen WC, Tsai Y, Wan L, Tsai FJ . Disease association of the CD103 polymorphisms in Taiwan Chinese Graves' ophthalmopathy patients . Ophthalmology . 117 . 8 . 1645–1651 . August 2010 . 20417566 . 10.1016/j.ophtha.2009.12.037 .
• Lesch KP, Timmesfeld N, Renner TJ, Halperin R, Röser C, Nguyen TT, Craig DW, Romanos J, Heine M, Meyer J, Freitag C, Warnke A, Romanos M, Schäfer H, Walitza S, Reif A, Stephan DA, Jacob C . Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies . Journal of Neural Transmission . 115 . 11 . 1573–1585 . November 2008 . 18839057 . 10.1007/s00702-008-0119-3 . 7036114 .
• Shiffman D, O'Meara ES, Bare LA, Rowland CM, Louie JZ, Arellano AR, Lumley T, Rice K, Iakoubova O, Luke MM, Young BA, Malloy MJ, Kane JP, Ellis SG, Tracy RP, Devlin JJ, Psaty BM . Association of gene variants with incident myocardial infarction in the Cardiovascular Health Study . Arteriosclerosis, Thrombosis, and Vascular Biology . 28 . 1 . 173–179 . January 2008 . 17975119 . 2636623 . 10.1161/ATVBAHA.107.153981 .
• Agace WW, Higgins JM, Sadasivan B, Brenner MB, Parker CM . T-lymphocyte-epithelial-cell interactions: integrin alpha(E)(CD103)beta(7), LEEP-CAM and chemokines . Current Opinion in Cell Biology . 12 . 5 . 563–568 . October 2000 . 10978890 . 10.1016/S0955-0674(00)00132-0 .
• Hadley G . Role of integrin CD103 in promoting destruction of renal allografts by CD8 T cells . American Journal of Transplantation . 4 . 7 . 1026–1032 . July 2004 . 15196058 . 10.1111/j.1600-6143.2004.00465.x . 3038018 . free .
• Enjuanes A, Benavente Y, Bosch F, Martín-Guerrero I, Colomer D, Pérez-Alvarez S, Reina O, Ardanaz MT, Jares P, García-Orad A, Pujana MA, Montserrat E, de Sanjosé S, Campo E . Genetic variants in apoptosis and immunoregulation-related genes are associated with risk of chronic lymphocytic leukemia . Cancer Research . 68 . 24 . 10178–10186 . December 2008 . 19074885 . 10.1158/0008-5472.CAN-08-2221 . free .
• Luke MM, O'Meara ES, Rowland CM, Shiffman D, Bare LA, Arellano AR, Longstreth WT, Lumley T, Rice K, Tracy RP, Devlin JJ, Psaty BM . Gene variants associated with ischemic stroke: the cardiovascular health study . Stroke . 40 . 2 . 363–368 . February 2009 . 19023099 . 2881155 . 10.1161/STROKEAHA.108.521328 .
• Silva LK, Blanton RE, Parrado AR, Melo PS, Morato VG, Reis EA, Dias JP, Castro JM, Vasconcelos PF, Goddard KA, Barreto ML, Reis MG, Teixeira MG . Dengue hemorrhagic fever is associated with polymorphisms in JAK1 . European Journal of Human Genetics . 18 . 11 . 1221–1227 . November 2010 . 20588308 . 2950898 . 10.1038/ejhg.2010.98 .
• Annacker O, Coombes JL, Malmstrom V, Uhlig HH, Bourne T, Johansson-Lindbom B, Agace WW, Parker CM, Powrie F . Essential role for CD103 in the T cell-mediated regulation of experimental colitis . The Journal of Experimental Medicine . 202 . 8 . 1051–1061 . October 2005 . 16216886 . 2213206 . 10.1084/jem.20040662 .
• Kilshaw PJ, Higgins JM . Alpha E: no more rejection? . The Journal of Experimental Medicine . 196 . 7 . 873–875 . October 2002 . 12370249 . 2194032 . 10.1084/jem.20021404 .
• Uss E, Rowshani AT, Hooibrink B, Lardy NM, van Lier RA, ten Berge IJ . CD103 is a marker for alloantigen-induced regulatory CD8+ T cells . Journal of Immunology . 177 . 5 . 2775–2783 . September 2006 . 16920912 . 10.4049/jimmunol.177.5.2775 . free .
• Le Floc'h A, Jalil A, Vergnon I, Le Maux Chansac B, Lazar V, Bismuth G, Chouaib S, Mami-Chouaib F . Alpha E beta 7 integrin interaction with E-cadherin promotes antitumor CTL activity by triggering lytic granule polarization and exocytosis . The Journal of Experimental Medicine . 204 . 3 . 559–570 . March 2007 . 17325197 . 2137907 . 10.1084/jem.20061524 .
• Heron M, Grutters JC, Van Moorsel CH, Ruven HJ, Kazemier KM, Claessen AM, Van den Bosch JM . Effect of variation in ITGAE on risk of sarcoidosis, CD103 expression, and chest radiography . Clinical Immunology . 133 . 1 . 117–125 . October 2009 . 19604725 . 10.1016/j.clim.2009.06.007 .
• Shaw SK, Brenner MB . The beta 7 integrins in mucosal homing and retention . Seminars in Immunology . 7 . 5 . 335–342 . October 1995 . 8580465 . 10.1016/1044-5323(95)90014-4 .
• Dickeson SK, Santoro SA . Ligand recognition by the I domain-containing integrins . Cellular and Molecular Life Sciences . 54 . 6 . 556–566 . June 1998 . 9676575 . 11147323 . 10.1007/s000180050184 . 9775686 .
• Heron M, Slieker WA, Zanen P, van Lochem EG, Hooijkaas H, van den Bosch JM, van Velzen-Blad H . Evaluation of CD103 as a cellular marker for the diagnosis of pulmonary sarcoidosis . Clinical Immunology . 126 . 3 . 338–344 . March 2008 . 18182176 . 10.1016/j.clim.2007.11.005 .

External links

• • Web site: ITGAE Orthologs . Cell Migration Consortium . https://web.archive.org/web/20141211173306/http://www.cellmigration.org/index.shtml . 2014-12-11 .

Notes and References

1. Kilshaw PJ, Higgins JM . Alpha E: no more rejection? . The Journal of Experimental Medicine . 196 . 7 . 873–875 . October 2002 . 12370249 . 2194032 . 10.1084/jem.20021404 .
2. Web site: Entrez Gene: integrin.
3. Lehmann J, Huehn J, de la Rosa M, Maszyna F, Kretschmer U, Krenn V, Brunner M, Scheffold A, Hamann A . Expression of the integrin alpha Ebeta 7 identifies unique subsets of CD25+ as well as CD25- regulatory T cells . Proceedings of the National Academy of Sciences of the United States of America . 99 . 20 . 13031–13036 . October 2002 . 12242333 . 130581 . 10.1073/pnas.192162899 . free . 2002PNAS...9913031L .
4. Aziz S, Fackler OT, Meyerhans A, Müller-Lantzsch N, Zeitz M, Schneider T . Replication of M-tropic HIV-1 in activated human intestinal lamina propria lymphocytes is the main reason for increased virus load in the intestinal mucosa . Journal of Acquired Immune Deficiency Syndromes . 38 . 1 . 23–30 . January 2005 . 15608520 . 10.1097/00126334-200501010-00005 . 22884381 . free .
5. Johansson-Lindbom B, Svensson M, Pabst O, Palmqvist C, Marquez G, Förster R, Agace WW . Functional specialization of gut CD103+ dendritic cells in the regulation of tissue-selective T cell homing . The Journal of Experimental Medicine . 202 . 8 . 1063–1073 . October 2005 . 16216890 . 2213212 . 10.1084/jem.20051100 .
6. Book: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW . WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (World Health Organization Classification of Tumours) . World Health Organization . Geneva . 2008 . 978-92-832-2431-0 . 4th .
7. Hadley GA, Bartlett ST, Via CS, Rostapshova EA, Moainie S . The epithelial cell-specific integrin, CD103 (alpha E integrin), defines a novel subset of alloreactive CD8+ CTL . Journal of Immunology . 159 . 8 . 3748–3756 . October 1997 . 9378961 . 10.4049/jimmunol.159.8.3748 . free .
8. Agace WW, Higgins JM, Sadasivan B, Brenner MB, Parker CM . T-lymphocyte-epithelial-cell interactions: integrin alpha(E)(CD103)beta(7), LEEP-CAM and chemokines . Current Opinion in Cell Biology . 12 . 5 . 563–568 . October 2000 . 10978890 . 10.1016/S0955-0674(00)00132-0 .
9. Kutlesa S, Wessels JT, Speiser A, Steiert I, Müller CA, Klein G . E-cadherin-mediated interactions of thymic epithelial cells with CD103+ thymocytes lead to enhanced thymocyte cell proliferation . Journal of Cell Science . 115 . Pt 23 . 4505–4515 . December 2002 . 12414996 . 10.1242/jcs.00142 . 14571087 .
10. Allakhverdi Z, Fitzpatrick D, Boisvert A, Baba N, Bouguermouh S, Sarfati M, Delespesse G . Expression of CD103 identifies human regulatory T-cell subsets . The Journal of Allergy and Clinical Immunology . 118 . 6 . 1342–1349 . December 2006 . 17137867 . 10.1016/j.jaci.2006.07.034 .