ICOSLG
ICOSLG | |||
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Identifiers | |||
Gene ontology | |||
Molecular function | |||
Cellular component | |||
Biological process | |||
Sources:Amigo / QuickGO |
Ensembl | |||||||||
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UniProt | |||||||||
RefSeq (mRNA) |
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RefSeq (protein) | |||||||||
Location (UCSC) | Chr 21: 44.22 – 44.24 Mb | Chr 10: 77.91 – 77.92 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
ICOS ligand is a protein that in humans is encoded by the ICOSLG gene[5][6][7] located at chromosome 21. ICOSLG has also been designated as CD275 (cluster of differentiation 275).
ICOSLG is glycosylated transmembrane structure, which is classified as a member of the
The interaction of ICOSLG with ICOS, the specific receptor for ICOSLG, is critically involved in the activation, proliferation, differentiation and cytokine production of T cells as well as in the antibody secretion from B cells during secondary immune responses.[8]
ICOSLG, which is extensively expressed in both non-lymphatic and
ICOSLG is also a major
Structure
Inducible costimulator-ligand (ICOS-L) is a member of the B7 family of costimulatory ligands
Both molecules have an identical
Interaction
Murine ICOSLG, unlike
The strong impact of ICOS/ICOSLG interaction on T cell-mediated immune responses in vivo became evident by the disruption of the ICOS gene in mice. ICOS deficient mice are characterized by impaired germinal center formation, have a profound defect in
Immunodeficiencies
The research with mutant ICOSLG showed that if the protein was retained in ER/GA, instead of the cell surface in normal case, it diminished B cell costimulation of T cells. It led to defect in antibody and memory B cell generation. Mutant ICOSLG also impaired migration of lymphocytes and neutrophils across endothelial cells, which normally express ICOSLG. These defects contributed with altered adaptive immunity and neutropenia in patient, thus showing ICOSLG deficiency as a cause of combined immunodeficiency.[15]
Immunotherapy
The fluctuant balance between co-stimulatory and coinhibitory signals that a T cell receives participates in the initiation, effection, and termination of an immune response. Excessive activation and immune reaction of T cells may result in autoimmune diseases and host immune injury.
ICOSLG delivers a potent co-stimulatory signal to T cells when engaged by ICOS, resulting in T cell activation and proliferation. The existence of ICOS/ICOSLG signal in vivo is closely associated with many mouse autoimmune disease models. Conversely, the absence of ICOS/ICOSLG signal may be a good way to relieve autoimmune disease. In view of its critical function in regulating immunohomeostasis, ICOS signaling has aroused great attention in immunodiagnosis and therapy.[8]
The ICOS/ICOSLG axis has been shown to promote either antitumor T cell responses (when activated in Th1 and other Teff) or protumor responses when triggered in
Undoubtedly, the development of more efficient and specific monoclonal antibodies may be important for further disclosure of ICOSLG function. Agonistic Abs are currently being administered either alone or in combination with immunotherapy and chemotherapy.[18]
References list
- ^ a b c GRCh38: Ensembl release 89: ENSG00000160223 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000000732 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 9734811.
- PMID 11007762.
- ^ "Entrez Gene: ICOSLG inducible T-cell co-stimulator ligand".
- ^ PMID 21851236.
- ^ PMID 11983910.
- S2CID 20542148.
- PMID 11023515.)
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: CS1 maint: DOI inactive as of March 2024 (link - PMID 11390480.
- S2CID 4360410.
- PMID 21530327.
- PMID 30498080.
- S2CID 4774208.
- PMID 38517331.
- PMID 32516116.
Further reading
- Flesch IE (2003). "Inducible costimulator-ligand (ICOS-L)". Journal of Biological Regulators and Homeostatic Agents. 16 (3): 217–219. PMID 12456022.
- Ling V, Wu PW, Finnerty HF, Bean KM, Spaulding V, Fouser LA, et al. (February 2000). "Cutting edge: identification of GL50, a novel B7-like protein that functionally binds to ICOS receptor". Journal of Immunology. 164 (4): 1653–1657. PMID 10657606.
- Aicher A, Hayden-Ledbetter M, Brady WA, Pezzutto A, Richter G, Magaletti D, et al. (May 2000). "Characterization of human inducible costimulator ligand expression and function". Journal of Immunology. 164 (9): 4689–4696. PMID 10779774.
- Wang S, Zhu G, Chapoval AI, Dong H, Tamada K, Ni J, Chen L (October 2000). "Costimulation of T cells by B7-H2, a B7-like molecule that binds ICOS". Blood. 96 (8): 2808–2813. PMID 11023515.
- Ling V, Wu PW, Miyashiro JS, Marusic S, Finnerty HF, Collins M (June 2001). "Differential expression of inducible costimulator-ligand splice variants: lymphoid regulation of mouse GL50-B and human GL50 molecules". Journal of Immunology. 166 (12): 7300–7308. PMID 11390480.
- Sperling AI, Bluestone JA (July 2001). "ICOS costimulation: It's not just for TH2 cells anymore". Nature Immunology. 2 (7): 573–574. S2CID 31317654.
- Wang S, Zhu G, Tamada K, Chen L, Bajorath J (April 2002). "Ligand binding sites of inducible costimulator and high avidity mutants with improved function". The Journal of Experimental Medicine. 195 (8): 1033–1041. PMID 11956294.
- Khayyamian S, Hutloff A, Büchner K, Gräfe M, Henn V, Kroczek RA, Mages HW (April 2002). "ICOS-ligand, expressed on human endothelial cells, costimulates Th1 and Th2 cytokine secretion by memory CD4+ T cells". Proceedings of the National Academy of Sciences of the United States of America. 99 (9): 6198–6203. PMID 11983910.
- Akbari O, Freeman GJ, Meyer EH, Greenfield EA, Chang TT, Sharpe AH, et al. (September 2002). "Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity". Nature Medicine. 8 (9): 1024–1032. S2CID 30454021.
- Kurosawa S, Myers AC, Chen L, Wang S, Ni J, Plitt JR, et al. (May 2003). "Expression of the costimulatory molecule B7-H2 (inducible costimulator ligand) by human airway epithelial cells". American Journal of Respiratory Cell and Molecular Biology. 28 (5): 563–573. PMID 12707012.
- Chen XL, Cao XD, Kang AJ, Wang KM, Su BS, Wang YL (June 2003). "In situ expression and significance of B7 costimulatory molecules within tissues of human gastric carcinoma". World Journal of Gastroenterology. 9 (6): 1370–1373. PMID 12800259.
- Iwai H, Abe M, Hirose S, Tsushima F, Tezuka K, Akiba H, et al. (September 2003). "Involvement of inducible costimulator-B7 homologous protein costimulatory pathway in murine lupus nephritis". Journal of Immunology. 171 (6): 2848–2854. PMID 12960306.
- Schreiner B, Wischhusen J, Mitsdoerffer M, Schneider D, Bornemann A, Melms A, et al. (December 2003). "Expression of the B7-related molecule ICOSL by human glioma cells in vitro and in vivo". Glia. 44 (3): 296–301. S2CID 25318238.
- Saatian B, Yu XY, Yu X, Lane AP, Doyle T, Casolaro V, Spannhake EW (July 2004). "Expression of genes for B7-H3 and other T cell ligands by nasal epithelial cells during differentiation and activation". American Journal of Physiology. Lung Cellular and Molecular Physiology. 287 (1): L217–L225. PMID 15047568.
- Nakazawa A, Dotan I, Brimnes J, Allez M, Shao L, Tsushima F, et al. (May 2004). "The expression and function of costimulatory molecules B7H and B7-H1 on colonic epithelial cells". Gastroenterology. 126 (5): 1347–1357. PMID 15131796.
External links
- ICOSLG+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)