ITGAE

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.^[5][6] 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).

ITGAE
Identifiers
Aliases	ITGAE, CD103, HUMINAE, integrin subunit alpha E
External IDs	OMIM: 604682; MGI: 1298377; HomoloGene: 113560; GeneCards: ITGAE; OMA:ITGAE - orthologs
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17p13.2 Start 3,714,628 bp[1] End 3,801,188 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 B4|11 45.22 cM Start 72,981,409 bp[2] End 73,038,272 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in oocyte secondary oocyte glutes muscle of arm biceps brachii putamen triceps brachii muscle caudate nucleus monocyte lymph node Top expressed in seminiferous tubule spermatid spermatocyte mesenteric lymph nodes Paneth cell lumbar subsegment of spinal cord blood jejunum thymus duodenum More reference expression data BioGPS n/a
Gene ontology Molecular function metal ion binding Cellular component integral component of membrane integrin complex plasma membrane external side of plasma membrane membrane Biological process integrin-mediated signaling pathway cell adhesion extracellular matrix organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3682 16407 Ensembl ENSG00000083457 ENSMUSG00000005947 UniProt P38570 Q60677 RefSeq (mRNA) NM_002208 NM_008399 NM_172944 NM_001361245 RefSeq (protein) NP_002199 NP_032425 NP_001348174 Location (UCSC) Chr 17: 3.71 – 3.8 Mb Chr 11: 72.98 – 73.04 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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).^[7] It has also been reported on lamina propria T cells.^[8] A subset of dendritic cells in the gut mucosa and mesenteric lymph nodes, known as CD103 dendritic cells, also expresses this marker.^[9]

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.^[10]

Function

The chief ligand for αEβ7 is E-cadherin, a cellular adhesion molecule (CAM) found on epithelial cells.^[11] It is probably important for T cell homing to the intestinal sites^[12] and thymocyte contacts with thymic reticuloepithelial cells.^[13]

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.^[14] 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

References

1. GRCh38: Ensembl release 89: ENSG00000083457 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000005947 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Kilshaw PJ, Higgins JM (October 2002). "Alpha E: no more rejection?". The Journal of Experimental Medicine. 196 (7): 873–875. doi:10.1084/jem.20021404. PMC 2194032. PMID 12370249.
6. "Entrez Gene: integrin".
7. Lehmann J, Huehn J, de la Rosa M, Maszyna F, Kretschmer U, Krenn V, et al. (October 2002). "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. Bibcode:2002PNAS...9913031L. doi:10.1073/pnas.192162899. PMC 130581. PMID 12242333.
8. Aziz S, Fackler OT, Meyerhans A, Müller-Lantzsch N, Zeitz M, Schneider T (January 2005). "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. doi:10.1097/00126334-200501010-00005. PMID 15608520. S2CID 22884381.
9. Johansson-Lindbom B, Svensson M, Pabst O, Palmqvist C, Marquez G, Förster R, et al. (October 2005). "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. doi:10.1084/jem.20051100. PMC 2213212. PMID 16216890.
10. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. (2008). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (World Health Organization Classification of Tumours) (4th ed.). Geneva: World Health Organization. ISBN 978-92-832-2431-0.
11. Hadley GA, Bartlett ST, Via CS, Rostapshova EA, Moainie S (October 1997). "The epithelial cell-specific integrin, CD103 (alpha E integrin), defines a novel subset of alloreactive CD8+ CTL". Journal of Immunology. 159 (8): 3748–3756. doi:10.4049/jimmunol.159.8.3748. PMID 9378961.
12. Agace WW, Higgins JM, Sadasivan B, Brenner MB, Parker CM (October 2000). "T-lymphocyte-epithelial-cell interactions: integrin alpha(E)(CD103)beta(7), LEEP-CAM and chemokines". Current Opinion in Cell Biology. 12 (5): 563–568. doi:10.1016/S0955-0674(00)00132-0. PMID 10978890.
13. Kutlesa S, Wessels JT, Speiser A, Steiert I, Müller CA, Klein G (December 2002). "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. doi:10.1242/jcs.00142. PMID 12414996. S2CID 14571087.
14. Allakhverdi Z, Fitzpatrick D, Boisvert A, Baba N, Bouguermouh S, Sarfati M, et al. (December 2006). "Expression of CD103 identifies human regulatory T-cell subsets". The Journal of Allergy and Clinical Immunology. 118 (6): 1342–1349. doi:10.1016/j.jaci.2006.07.034. PMID 17137867.

Further reading

• Davila S, Froeling FE, Tan A, Bonnard C, Boland GJ, Snippe H, et al. (April 2010). "New genetic associations detected in a host response study to hepatitis B vaccine". Genes and Immunity. 11 (3): 232–238. doi:10.1038/gene.2010.1. PMID 20237496.
• Tilburgs T, Scherjon SA, Roelen DL, Claas FH (February 2009). "Decidual CD8+CD28- T cells express CD103 but not perforin". Human Immunology. 70 (2): 96–100. doi:10.1016/j.humimm.2008.12.006. PMID 19150377.
• Schlickum S, Sennefelder H, Friedrich M, Harms G, Lohse MJ, Kilshaw P, et al. (August 2008). "Integrin alpha E(CD103)beta 7 influences cellular shape and motility in a ligand-dependent fashion". Blood. 112 (3): 619–625. doi:10.1182/blood-2008-01-134833. PMID 18492951.
• Rose JE, Behm FM, Drgon T, Johnson C, Uhl GR (2010). "Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score". Molecular Medicine. 16 (7–8): 247–253. doi:10.2119/molmed.2009.00159. PMC 2896464. PMID 20379614.
• Liu YH, Chen RH, Chen WC, Tsai Y, Wan L, Tsai FJ (August 2010). "Disease association of the CD103 polymorphisms in Taiwan Chinese Graves' ophthalmopathy patients". Ophthalmology. 117 (8): 1645–1651. doi:10.1016/j.ophtha.2009.12.037. PMID 20417566.
• Lesch KP, Timmesfeld N, Renner TJ, Halperin R, Röser C, Nguyen TT, et al. (November 2008). "Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies". Journal of Neural Transmission. 115 (11): 1573–1585. doi:10.1007/s00702-008-0119-3. PMID 18839057. S2CID 7036114.
• Shiffman D, O'Meara ES, Bare LA, Rowland CM, Louie JZ, Arellano AR, et al. (January 2008). "Association of gene variants with incident myocardial infarction in the Cardiovascular Health Study". Arteriosclerosis, Thrombosis, and Vascular Biology. 28 (1): 173–179. doi:10.1161/ATVBAHA.107.153981. PMC 2636623. PMID 17975119.
• Agace WW, Higgins JM, Sadasivan B, Brenner MB, Parker CM (October 2000). "T-lymphocyte-epithelial-cell interactions: integrin alpha(E)(CD103)beta(7), LEEP-CAM and chemokines". Current Opinion in Cell Biology. 12 (5): 563–568. doi:10.1016/S0955-0674(00)00132-0. PMID 10978890.
• Hadley G (July 2004). "Role of integrin CD103 in promoting destruction of renal allografts by CD8 T cells". American Journal of Transplantation. 4 (7): 1026–1032. doi:10.1111/j.1600-6143.2004.00465.x. PMID 15196058. S2CID 3038018.
• Enjuanes A, Benavente Y, Bosch F, Martín-Guerrero I, Colomer D, Pérez-Alvarez S, et al. (December 2008). "Genetic variants in apoptosis and immunoregulation-related genes are associated with risk of chronic lymphocytic leukemia". Cancer Research. 68 (24): 10178–10186. doi:10.1158/0008-5472.CAN-08-2221. PMID 19074885.
• Luke MM, O'Meara ES, Rowland CM, Shiffman D, Bare LA, Arellano AR, et al. (February 2009). "Gene variants associated with ischemic stroke: the cardiovascular health study". Stroke. 40 (2): 363–368. doi:10.1161/STROKEAHA.108.521328. PMC 2881155. PMID 19023099.
• Silva LK, Blanton RE, Parrado AR, Melo PS, Morato VG, Reis EA, et al. (November 2010). "Dengue hemorrhagic fever is associated with polymorphisms in JAK1". European Journal of Human Genetics. 18 (11): 1221–1227. doi:10.1038/ejhg.2010.98. PMC 2950898. PMID 20588308.
• Annacker O, Coombes JL, Malmstrom V, Uhlig HH, Bourne T, Johansson-Lindbom B, et al. (October 2005). "Essential role for CD103 in the T cell-mediated regulation of experimental colitis". The Journal of Experimental Medicine. 202 (8): 1051–1061. doi:10.1084/jem.20040662. PMC 2213206. PMID 16216886.
• Kilshaw PJ, Higgins JM (October 2002). "Alpha E: no more rejection?". The Journal of Experimental Medicine. 196 (7): 873–875. doi:10.1084/jem.20021404. PMC 2194032. PMID 12370249.
• Uss E, Rowshani AT, Hooibrink B, Lardy NM, van Lier RA, ten Berge IJ (September 2006). "CD103 is a marker for alloantigen-induced regulatory CD8+ T cells". Journal of Immunology. 177 (5): 2775–2783. doi:10.4049/jimmunol.177.5.2775. PMID 16920912.
• Le Floc'h A, Jalil A, Vergnon I, Le Maux Chansac B, Lazar V, Bismuth G, et al. (March 2007). "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. doi:10.1084/jem.20061524. PMC 2137907. PMID 17325197.
• Heron M, Grutters JC, Van Moorsel CH, Ruven HJ, Kazemier KM, Claessen AM, et al. (October 2009). "Effect of variation in ITGAE on risk of sarcoidosis, CD103 expression, and chest radiography". Clinical Immunology. 133 (1): 117–125. doi:10.1016/j.clim.2009.06.007. PMID 19604725.
• Shaw SK, Brenner MB (October 1995). "The beta 7 integrins in mucosal homing and retention". Seminars in Immunology. 7 (5): 335–342. doi:10.1016/1044-5323(95)90014-4. PMID 8580465.
• Dickeson SK, Santoro SA (June 1998). "Ligand recognition by the I domain-containing integrins". Cellular and Molecular Life Sciences. 54 (6): 556–566. doi:10.1007/s000180050184. PMC 11147323. PMID 9676575. S2CID 9775686.
• Heron M, Slieker WA, Zanen P, van Lochem EG, Hooijkaas H, van den Bosch JM, et al. (March 2008). "Evaluation of CD103 as a cellular marker for the diagnosis of pulmonary sarcoidosis". Clinical Immunology. 126 (3): 338–344. doi:10.1016/j.clim.2007.11.005. PMID 18182176.

External links

• ITGAE+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• "ITGAE Orthologs". Cell Migration Consortium. Archived from the original on 2014-12-11.