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CD1D

From Wikipedia, the free encyclopedia

CD1D
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCD1D, CD1A, R3, R3G1, CD1d molecule
External IDsOMIM: 188410; MGI: 107674; HomoloGene: 1337; GeneCards: CD1D; OMA:CD1D - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001766
NM_001319145
NM_001371761
NM_001371762
NM_001371763

NM_007639
NM_001379501
NM_001379502
NM_001379503

RefSeq (protein)

NP_001306074
NP_001757
NP_001358690
NP_001358691
NP_001358692

NP_031665
NP_001366430
NP_001366431
NP_001366432

Location (UCSC)Chr 1: 158.18 – 158.19 MbChr 3: 86.9 – 86.91 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

CD1D is the human gene that encodes the protein CD1d,[5] a member of the CD1 (cluster of differentiation 1) family of glycoproteins expressed on the surface of various human antigen-presenting cells. They are non-classical MHC proteins, related to the class I MHC proteins, and are involved in the presentation of lipid antigens to T cells. CD1d is the only member of the group 2 CD1 molecules.

Biological significance

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CD1d-presented lipid antigens activate a special class of T cells, known as natural killer T (NKT) cells, through the interaction with the T-cell receptor present on NKT membranes.[5] When activated, NKT cells rapidly produce Th1 and Th2 cytokines, typically represented by interferon-gamma and interleukin 4 production.

Nomenclature

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CD1d is also known as R3G1

Ligands

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Some of the known ligands for CD1d are:

Tetramers

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CD1d tetramers are protein constructs composed of four CD1d molecules joined together and usually fluorescently labelled, used to identify NKT cells or other CD1d-reactive cells. In particular, type I NKT cells and some type II NKT cells are stained by them. A differentiation of these two types can be obtained in human by using an antibody against the TCR Vα24 chain, which is specific of type I NKT cells.[10]

Although they are the most widely used of CD1d oligomers, sometimes CD1d dimers (two units) or pentamers (five units) are used instead.[10]

In obesity and type 2 diabetes

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In obesity, NKT cells exhibit both an inflammatory and anti-inflammatory function. On the one hand, they release IFN-γ, but on the other hand, they reduce inflammation via the production of IL-4 and -10.[11]

Despite the anti-inflammatory cytokines released by NKT cells, the overall effect of CD1d and NKT cells is that of mediating the inflammation caused by diet-induced obesity. Adipocyte-specific CD1d knock-out mice, when fed a high-fat diet, are protected from obesity and exhibit reduced adipose tissue inflammation. [12]

Obesity itself also decreases the expression of CD1d, and mice fed a high-fat diet showed reduced levels of CD1d expression in adipocytes after 16 weeks. These data suggest that differentiated adipocytes could act as antigen-presenting cells for adipose iNKT cells and that reduced expression of CD1d might be associated with iNKT cells that have been dysregulated following diet-induced obesity.[13]

Research from 2004 showed that iNKT cell counts may be reduced in diabetes type II. Transgenic non-obese mice in which CD1d molecules were overexpressed under the control of the insulin promoter within the pancreatic islets exhibited restored function of NKT cells as immunoregulatory. Diabetes was prevented in these transgenic mice.[14]

CD1d has been shown to play an important role in metabolic biological processes, such as retinol metabolism and steroid hormone biosynthesis process activation. There is research that suggests a connection between the impaired activity of CD1d and MASLD. One study showed that feeding CD1d knock-out mice a high-fat diet impaired lipid metabolism in the liver.[15]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000158473Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028076Ensembl, 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. ^ a b "P15813 (CD1D_HUMAN)". Uniprot. Retrieved 1 March 2013.
  6. ^ Franck RW (January 2012). "C-Galactosylceramide: Synthesis and Immunology". Comptes Rendus. Chimie. 15 (1): 46–56. doi:10.1016/j.crci.2011.05.006. PMC 3293403. PMID 22408579.
  7. ^ Bendelac A, Savage PB, Teyton L (2007). "The biology of NKT cells". Annual Review of Immunology. 25 (1): 297–336. doi:10.1146/annurev.immunol.25.022106.141711. PMID 17150027.
  8. ^ Zhou D (August 2006). "The immunological function of iGb3". Current Protein & Peptide Science. 7 (4): 325–333. doi:10.2174/138920306778018007. PMID 16918447.
  9. ^ Kerzerho J, Yu ED, Barra CM, Alari-Pahissa E, Girardi E, Harrak Y, et al. (March 2012). "Structural and functional characterization of a novel nonglycosidic type I NKT agonist with immunomodulatory properties". Journal of Immunology. 188 (5): 2254–2265. doi:10.4049/jimmunol.1103049. PMC 3288653. PMID 22301545.
  10. ^ a b Terabe M, Berzofsky JA (2008). "The role of NKT cells in tumor immunity". Advances in Cancer Research. 101: 277–348. doi:10.1016/S0065-230X(08)00408-9. PMC 2693255. PMID 19055947.
  11. ^ Satoh M, Iwabuchi K (2018). "Role of Natural Killer T Cells in the Development of Obesity and Insulin Resistance: Insights From Recent Progress". Frontiers in Immunology. 9: 1314. doi:10.3389/fimmu.2018.01314. PMC 6004523. PMID 29942311.
  12. ^ Satoh M, Hoshino M, Fujita K, Iizuka M, Fujii S, Clingan CS, et al. (June 2016). "Adipocyte-specific CD1d-deficiency mitigates diet-induced obesity and insulin resistance in mice". Scientific Reports. 6 (1): 28473. Bibcode:2016NatSR...628473S. doi:10.1038/srep28473. PMC 4916414. PMID 27329323.
  13. ^ Huh JY, Park J, Kim JI, Park YJ, Lee YK, Kim JB (April 2017). "Deletion of CD1d in Adipocytes Aggravates Adipose Tissue Inflammation and Insulin Resistance in Obesity". Diabetes. 66 (4): 835–847. doi:10.2337/db16-1122. PMID 28082459.
  14. ^ Falcone M, Facciotti F, Ghidoli N, Monti P, Olivieri S, Zaccagnino L, et al. (May 2004). "Up-regulation of CD1d expression restores the immunoregulatory function of NKT cells and prevents autoimmune diabetes in nonobese diabetic mice". Journal of Immunology. 172 (10): 5908–5916. doi:10.4049/jimmunol.172.10.5908. PMID 15128771.
  15. ^ Zheng Q, Xue C, Gu X, Shan D, Chu Q, Wang J, et al. (2022-04-08). "Multi-Omics Characterizes the Effects and Mechanisms of CD1d in Nonalcoholic Fatty Liver Disease Development". Frontiers in Cell and Developmental Biology. 10: 830702. doi:10.3389/fcell.2022.830702. PMC 9024148. PMID 35465315.

Further reading

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