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, etal . New genetic associations detected in a host response study to hepatitis B vaccine. . Genes Immun. . 11 . 3 . 232–8 . 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. . Hum. Immunol. . 70 . 2 . 96–100 . 2009 . 19150377 . 10.1016/j.humimm.2008.12.006 .
• Schlickum S, Sennefelder H, Friedrich M, etal . Integrin alpha E(CD103)beta 7 influences cellular shape and motility in a ligand-dependent fashion. . Blood . 112 . 3 . 619–25 . 2008 . 18492951 . 10.1182/blood-2008-01-134833 . free .
• Rose JE, Behm FM, Drgon T, etal . Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. . Mol. Med. . 16 . 7–8 . 247–53 . 2010. 20379614 . 10.2119/molmed.2009.00159 . 2896464.
• Liu YH, Chen RH, Chen WC, etal . Disease association of the CD103 polymorphisms in Taiwan Chinese Graves' ophthalmopathy patients . Ophthalmology . 117 . 8 . 1645–51 . 2010 . 20417566 . 10.1016/j.ophtha.2009.12.037 .
• Lesch KP, Timmesfeld N, Renner TJ, etal . Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies . J Neural Transm . 115 . 11 . 1573–85 . 2008 . 18839057 . 10.1007/s00702-008-0119-3 . 7036114 .
• Shiffman D, O'Meara ES, Bare LA, etal . Association of gene variants with incident myocardial infarction in the Cardiovascular Health Study . Arterioscler. Thromb. Vasc. Biol. . 28 . 1 . 173–9 . 2008 . 17975119 . 10.1161/ATVBAHA.107.153981 . 2636623.
• Agace WW, Higgins JM, Sadasivan B, etal . T-lymphocyte-epithelial-cell interactions: integrin alpha(E)(CD103)beta(7), LEEP-CAM and chemokines . Curr. Opin. Cell Biol. . 12 . 5 . 563–8 . 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 . Am. J. Transplant. . 4 . 7 . 1026–32 . 2004 . 15196058 . 10.1111/j.1600-6143.2004.00465.x . 3038018 . free .
• Enjuanes A, Benavente Y, Bosch F, etal . Genetic variants in apoptosis and immunoregulation-related genes are associated with risk of chronic lymphocytic leukemia . Cancer Res. . 68 . 24 . 10178–86 . 2008 . 19074885 . 10.1158/0008-5472.CAN-08-2221 . free .
• Luke MM, O'Meara ES, Rowland CM, etal . Gene variants associated with ischemic stroke: the cardiovascular health study . Stroke . 40 . 2 . 363–8 . 2009 . 19023099 . 10.1161/STROKEAHA.108.521328 . 2881155.
• Silva LK, Blanton RE, Parrado AR, etal . Dengue hemorrhagic fever is associated with polymorphisms in JAK1 . Eur. J. Hum. Genet. . 18 . 11 . 1221–7 . 2010 . 20588308 . 2950898 . 10.1038/ejhg.2010.98 .
• Annacker O, Coombes JL, Malmstrom V, etal . Essential role for CD103 in the T cell-mediated regulation of experimental colitis . J. Exp. Med. . 202 . 8 . 1051–61 . 2005 . 16216886 . 2213206 . 10.1084/jem.20040662 .
• Kilshaw PJ, Higgins JM . Alpha E: no more rejection? . J. Exp. Med. . 196 . 7 . 873–5 . 2002 . 12370249 . 10.1084/jem.20021404 . 2194032.
• Uss E, Rowshani AT, Hooibrink B, etal . CD103 is a marker for alloantigen-induced regulatory CD8+ T cells . J. Immunol. . 177 . 5 . 2775–83 . 2006 . 16920912 . 10.4049/jimmunol.177.5.2775. free .
• Le Floc'h A, Jalil A, Vergnon I, etal . Alpha E beta 7 integrin interaction with E-cadherin promotes antitumor CTL activity by triggering lytic granule polarization and exocytosis . J. Exp. Med. . 204 . 3 . 559–70 . 2007 . 17325197 . 2137907 . 10.1084/jem.20061524 .
• Heron M, Grutters JC, Van Moorsel CH, etal . Effect of variation in ITGAE on risk of sarcoidosis, CD103 expression, and chest radiography . Clin. Immunol. . 133 . 1 . 117–25 . 2009 . 19604725 . 10.1016/j.clim.2009.06.007 .
• Shaw SK, Brenner MB . The beta 7 integrins in mucosal homing and retention . Semin. Immunol. . 7 . 5 . 335–42 . 1995 . 8580465 . 10.1016/1044-5323(95)90014-4 .
• Dickeson SK, Santoro SA . Ligand recognition by the I domain-containing integrins . Cell. Mol. Life Sci. . 54 . 6 . 556–66 . 1998 . 9676575 . 10.1007/s000180050184. 9775686 . 11147323 .
• Heron M, Slieker WA, Zanen P, etal . Evaluation of CD103 as a cellular marker for the diagnosis of pulmonary sarcoidosis . Clin. Immunol. . 126 . 3 . 338–44 . 2008 . 18182176 . 10.1016/j.clim.2007.11.005 .

External links

• • ITGAE Info with links in the Cell Migration Gateway

Notes and References

1. Kilshaw PJ, Higgins JM . Alpha E: no more rejection? . J. Exp. Med. . 196 . 7 . 873–5 . 2002 . 12370249 . 10.1084/jem.20021404 . 2194032 .
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 . Proc. Natl. Acad. Sci. U.S.A. . 99 . 20 . 13031–6 . October 2002 . 12242333 . 130581 . 10.1073/pnas.192162899 . 2002PNAS...9913031L . free .
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 . J. Acquir. Immune Defic. Syndr. . 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 . J. Exp. Med. . 202 . 8 . 1063–73 . 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 . J. Immunol. . 159 . 8 . 3748–56 . October 1997 . 10.4049/jimmunol.159.8.3748 . 9378961 . 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 . Curr. Opin. Cell Biol. . 12 . 5 . 563–8 . October 2000 . 10978890 . 10.1016/S0955-0674(00)00132-0.
9. Kutleša. Snježana. Wessels. Johannes T.. Speiser. Angelika. Steiert. Inge. Müller. Claudia A.. Klein. Gerd. 2002-12-01. E-cadherin-mediated interactions of thymic epithelial cells with CD103+ thymocytes lead to enhanced thymocyte cell proliferation. Journal of Cell Science. en. 115. 23. 4505–4515. 10.1242/jcs.00142. 12414996 . 14571087 . 1477-9137.
10. Allakhverdi Z, Fitzpatrick D, Boisvert A, Baba N, Bouguermouh S, Sarfati M, Delespesse G . Expression of CD103 identifies human regulatory T-cell subsets . J. Allergy Clin. Immunol. . 118 . 6 . 1342–9 . December 2006 . 17137867 . 10.1016/j.jaci.2006.07.034 .