Functional evaluation of the role of C-type lectin domain family 16A at the chromosome 16p13 locus
Open accessAbstract
The type 1 diabetes-associated 16p13 locus contains the CLEC16A gene. Its preferential immune cell expression suggests involvement in autoimmunity. Given its elevated expression in dendritic and B cells - known professional antigen-presenting cells (APCs) - we hypothesize that C-type lectin domain family 16 member A (CLEC16A) may be involved in T cell co-stimulation and consequent activation and proliferation. We also sought to identify CLEC16A's subcellular localization. The effect of the CLEC16A knock-down (KD) on B cell co-stimulation and activation of T cells was tested in human lymphoblastoid cell lines (LCLs) by co-culture with CD4(+) T cells. T cell activation and proliferation were determined by flow-cytometric analysis of CD69 and CD25 expression and carboxyfluorescein succinimidyl ester (CFSE) dilution, respectively. CLEC16A subcellular localization in K562 cells was examined by immunofluorescence. We show that the CLEC16A KD did not affect the tested indices of lymphoblastoid cell line (LCL) APC capacity. Additionally, the percentage of activated T cells following LCL co-culture was not affected significantly by the CLEC16A KD. T cells co-cultured with KD or control LCLs also exhibited similar cell division profiles. CLEC16A co-localized with an endoplasmic reticulum (ER) marker, suggesting that it may be an ER protein. In conclusion, CLEC16A may not be involved in T cell co-stimulation. Additional studies on CLEC16A, accounting for its ER localization, are needed…
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These data are similar to those obtained upon CLEC16A siRNA knockdown in human B cells serving as antigen presenting cells.
“These data are similar to those obtained upon CLEC16A siRNA knockdown in human B cells serving as antigen presenting cells34.”
From Clec16a is Critical for Autolysosome Function and Purkinje Cell Survival (2016) · cites this paper as [34]
Cites
The Pfam Protein Families Database
Bateman, A. G. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.1.276 · Cited by 14,062 · see citing works
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
The Wellcome Trust Case Control Consortium, Management Committee, Burton, P. R., Clayton, D. G., Cardon, L. R., Craddock, N., Deloukas, P., Duncanson, A., Kwiatkowski, D. P., McCarthy, M. I., et al. (2007) · Nature · doi:10.1038/nature05911 · Cited by 9,442 · see citing works
SignalP 4.0: discriminating signal peptides from transmembrane regions
Petersen, T. N., Brunak, S., von Heijne, G., & Nielsen, H. (2011) · Nature Methods · doi:10.1038/nmeth.1701 · Cited by 8,847 · see citing works
The International HapMap Project
†The International HapMap Consortium, Genotyping centres: Baylor College of Medicine and ParAllele BioScience, Gibbs, R. A., Belmont, J. W., Hardenbol, P., Willis, T. D., Yu, F., Chinese HapMap Consortium, Yang, H., Ch'ang, L.-Y., et al. (2003) · Nature · doi:10.1038/nature02168 · Cited by 6,057 · see citing works
WoLF PSORT: protein localization predictor
Horton, P., Park, K., Obayashi, T., Fujita, N., Harada, H., Adams-Collier, C. J., & Nakai, K. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm259 · Cited by 4,154 · see citing works
CD28/B7 SYSTEM OF T CELL COSTIMULATION
Lenschow, D. J., Walunas, T. L., & Bluestone, J. A. (1996) · Annual Review of Immunology · doi:10.1146/annurev.immunol.14.1.233 · Cited by 2,717 · see citing works
The Pfam protein families database
Finn, R. D., Mistry, J., Tate, J., Coggill, P., Heger, A., Pollington, J. E., Gavin, O. L., Gunasekaran, P., Ceric, G., Forslund, K., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkp985 · Cited by 2,694 · see citing works
Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study
(2007) · New England Journal of Medicine · doi:10.1056/nejmoa073493 · Cited by 1,746 · see citing works
The Type 1 Diabetes Genetics Consortium, Barrett, J. C., Clayton, D. G., Concannon, P., Akolkar, B., Cooper, J. D., Erlich, H. A., Julier, C., Morahan, G., Nerup, J., et al. (2009) · Nature Genetics · doi:10.1038/ng.381 · Cited by 1,746 · see citing works
Large-scale analysis of the human and mouse transcriptomes
Su, A. I., Cooke, M. P., Ching, K. A., Hakak, Y., Walker, J. R., Wiltshire, T., Orth, A. P., Vega, R. G., Sapinoso, L. M., Moqrich, A., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.012025199 · Cited by 1,466 · see citing works
Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes
Finland, G. O. T. 1. D. I., Todd, J. A., the Wellcome Trust Case Control Consortium, Walker, N. M., Cooper, J. D., Smyth, D. J., Downes, K., Plagnol, V., Bailey, R., Nejentsev, S., et al. (2007) · Nature Genetics · doi:10.1038/ng2068 · Cited by 1,456 · see citing works
BioGPS: an extensible and customizable portal for querying and organizing gene annotation resources
Wu, C., Orozco, C., Boyer, J., Leglise, M., Goodale, J., Batalov, S., Hodge, C. L., Haase, J., Janes, J. O., Huss, J. W., et al. (2009) · Genome biology · doi:10.1186/gb-2009-10-11-r130 · Cited by 1,374 · see citing works
The Biochemistry and Cell Biology of Antigen Processing and Presentation
Germain, R. N., & Margulies, D. H. (1993) · Annual Review of Immunology · doi:10.1146/annurev.iy.11.040193.002155 · Cited by 1,017 · see citing works
Nejentsev, S., Walker, N., Riches, D., Egholm, M., & Todd, J. A. (2009) · Science · doi:10.1126/science.1167728 · Cited by 958 · see citing works
PROSITE, a protein domain database for functional characterization and annotation
Sigrist, C. J. A., Cerutti, L., de Castro, E., Langendijk-Genevaux, P. S., Bulliard, V., Bairoch, A., & Hulo, N. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp885 · Cited by 852 · see citing works
Assembly, Transport, and Function of MHC Class II Molecules
Cresswell, P. (1994) · Annual Review of Immunology · doi:10.1146/annurev.iy.12.040194.001355 · Cited by 809 · see citing works
Assessing the role of HLA-linked and unlinked determinants of disease.
RISCH, N. J. (1987) · PubMed · Cited by 542 · see citing works
A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene
Hakonarson, H., Grant, S. F. A., Bradfield, J. P., Marchand, L., Kim, C. E., Glessner, J. T., Grabs, R., Casalunovo, T., Taback, S. P., Frackelton, E. C., et al. (2007) · Nature · doi:10.1038/nature06010 · Cited by 542 · see citing works
Self-citationLanier, L. L., O'Fallon, S., Somoza, C., Phillips, J. H., Linsley, P. S., Okumura, K., Ito, D., & Azuma, M. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.154.1.97 · Cited by 480 · see citing works
Retention and retrieval in the endoplasmic reticulum and the Golgi apparatus
Nilsson, T., & Warren, G. W. (1994) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(94)90070-1 · Cited by 247 · see citing works
Simms, P. E., & Ellis, T. (1996) · Clinical and Diagnostic Laboratory Immunology · doi:10.1128/cdli.3.3.301-304.1996 · Cited by 210 · see citing works
Underhill, D. M., & Goodridge, H. S. (2007) · Trends in Immunology · doi:10.1016/j.it.2006.12.004 · Cited by 190 · see citing works
Natural killer cells distinguish innocuous and destructive forms of pancreatic islet autoimmunity
Poirot, L., Benoist, C. O., & Mathis, D. J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402065101 · Cited by 173 · see citing works
Schurgers, E., Kelchtermans, H., Mitera, T., Geboes, L., & Matthys, P. (2010) · Arthritis Research & Therapy · doi:10.1186/ar2939 · Cited by 168 · see citing works
The expanding genetic overlap between multiple sclerosis and type I diabetes
Booth, D. R., Heard, R. N., Stewart, G. J., Goris, A., Dobosi, R., Dubois, B., Lorentzen, Å. R., Celius, E. G., Harbo, H. F., Spurkland, A., et al. (2008) · Genes and Immunity · doi:10.1038/gene.2008.83 · Cited by 168 · see citing works
Altered Natural Killer Cells in Type 1 Diabetic Patients
Rodacki, M., Svoren, B. M., Butty, V. L., Besse, W., Laffel, L. M., Benoist, C. O., & Mathis, D. J. (2006) · Diabetes · doi:10.2337/db06-0493 · Cited by 163 · see citing works
High-performance signal peptide prediction based on sequence alignment techniques
Frank, K., & Sippl, M. J. (2008) · Bioinformatics · doi:10.1093/bioinformatics/btn422 · Cited by 135 · see citing works
A Human Type 1 Diabetes Susceptibility Locus Maps to Chromosome 21q22.3
CONCANNON, P. J., Önengüt-Gümüşcü, S., Todd, J. A., Smyth, D. J., Pociot, F., Bergholdt, R., Akolkar, B., Erlich, H. A., Hilner, J. E., Julier, C., et al. (2008) · Diabetes · doi:10.2337/db08-0753 · Cited by 130 · see citing works
Polymorphisms inCLEC16AandCIITAat 16p13 Are Associated with Primary Adrenal Insufficiency
Skinningsrud, B., Husebye, E. S., Pearce, S. H. S., McDonald, D., Brandal, K., Wolff, A. S. B., Løvås, K., Egeland, T., & Undlien, D. E. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0821 · Cited by 119 · see citing works
Davison, L. J., Wallace, C., Cooper, J. D., Cope, N. F., Wilson, N. K., Smyth, D. J., Howson, J. M. M., Saleh, N. M., Aljeffery, A., Angus, K. L., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr468 · Cited by 107 · see citing works
Mardiney, M. R., Brown, M. R., & Fleisher, T. A. (1996) · Cytometry · doi:10.1002/(sici)1097-0320(19961215)26:4 · Cited by 105 · see citing works
RNA interference: learning gene knock-down from cell physiology
D, S. M. M., & Provenzano, M. (2004) · Journal of Translational Medicine · doi:10.1186/1479-5876-2-39 · Cited by 102 · see citing works
Schultz, N., Marenstein, D. R., de Angelis, D. D., Wang, W.-Q., Nelander, S., Jacobsen, A., Marks, D., Massagué, J., & Sander, C. (2011) · Silence · doi:10.1186/1758-907x-2-3 · Cited by 93 · see citing works
Kim, S., Wairkar, Y. P., Daniels, R. W., & DiAntonio, A. (2010) · Journal of Cell Biology · doi:10.1083/jcb.200911126 · Cited by 82 · see citing works
B cells as effectors and regulators of autoimmunity
Mariño, E., & Grey, S. T. (2012) · Autoimmunity · doi:10.3109/08916934.2012.665527 · Cited by 72 · see citing works
Antigen presentation events in autoimmune diabetes
Calderón, B., & Unanue, E. R. (2011) · Current Opinion in Immunology · doi:10.1016/j.coi.2011.11.005 · Cited by 65 · see citing works
Chromosomal region 16p13: further evidence of increased predisposition to immune diseases
Martínez, A., Perdigones, N., Cénit, M. C., Espino‐Paisán, L., Varadé, J., Lamas, J. R., Santiago, J. L., Fernández‐Arquero, M., de la Calle, H., Arroyo, R., et al. (2009) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2008.098376 · Cited by 61 · see citing works
Awata, T., Kawasaki, E., Tanaka, S. A., Ikegami, H., Maruyama, T., Shimada, A., Nakanishi, K., Kobayashi, T., Iizuka, H., Uga, M., et al. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0718 · Cited by 52 · see citing works
Mero, I.-L., Ban, M., Lorentzen, Å. R., Smestad, C., Celius, E. G., Sæther, H. S., Saeedi, H., Viken, M. K., Skinningsrud, B., Undlien, D. E., et al. (2010) · Genes and Immunity · doi:10.1038/gene.2010.59 · Cited by 44 · see citing works
Leikfoss, I. S., Mero, I.-L., Dahle, M. K., Lie, B. A., Harbo, H. F., Spurkland, A., & Berge, T. (2012) · Genes and Immunity · doi:10.1038/gene.2012.52 · Cited by 40 · see citing works
Involvement of CLEC16A in Activation of Astrocytes After LPS Treated
Wu, X., Li, J., Chen, C., Yan, Y., Jiang, S., Wu, X., Shao, B., Xu, J., Kang, L., Huang, Y., et al. (2011) · Neurochemical Research · doi:10.1007/s11064-011-0581-4 · Cited by 21 · see citing works
Wu, X., Zhu, X., Wang, X., Ma, J., Zhu, S., Li, J., & Liu, Y. (2008) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2008.03437.x · Cited by 19 · see citing works
Punzón, C., Resino, S., Bellón, J. M., Muñoz‐Fernández, M. Á., & Fresno, M. (2002) · PubMed · Cited by 5 · see citing works
Quantitation of T cell depletion by limiting dilution analysis.
Moretti, L., Corpuz, S., Giuliodori, L., Stramigioli, S., & Pj, M. (1991) · PubMed · Cited by 2 · see citing works
Flagged first, then by citations
1 of the 45 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Ormerod, 2008, Cell proliferation, 80
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Genetic risk factors for type 1 diabetes
Pociot, F., & Lernmark, Å. (2016) · The Lancet · doi:10.1016/s0140-6736(16)30582-7 · Cited by 553 · see citing works
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Soleimanpour, S. A., Gupta, A., Bakay, M., Ferrari, A. M., Groff, D. N., Fadista, J., Spruce, L. A., Kushner, J. A., Groop, L., Seeholzer, S. H., et al. (2014) · Cell · doi:10.1016/j.cell.2014.05.016 · Cited by 211 · see citing works
Li, J., Jørgensen, S. F., Maggadottir, S. M., Bakay, M. A., Warnatz, K., Glessner, J., Pandey, R., Salzer, U., Schmidt, R. E., Pérez, E., et al. (2015) · Nature Communications · doi:10.1038/ncomms7804 · Cited by 72 · see citing works
Multiple sclerosis-associated CLEC16A controls HLA class II expression via late endosome biogenesis
van Luijn, M. M., Kreft, K. L., Jongsma, M. L., Mes, S. W., Wierenga-Wolf, A. F., van Meurs, M., Melief, M.-J., der Kant, R. V., Janssen, L., Janssen, H., et al. (2015) · Brain · doi:10.1093/brain/awv080 · Cited by 68 · see citing works
Human CLEC16A regulates autophagy through modulating mTOR activity
Tam, R. C. Y., Li, M., Gao, Y., Pang, Y. T., Yan, S., Ge, W., Lau, C. S., & Chan, V. S. F. (2017) · Experimental Cell Research · doi:10.1016/j.yexcr.2017.02.017 · Cited by 32 · see citing works
Clec16a is Critical for Autolysosome Function and Purkinje Cell Survival
Redmann, V., Lamb, C. A., Hwang, S., Orchard, R. C., Kim, S., Razi, M., Milam, A., Park, S., Yokoyama, C. C., Kambal, A., et al. (2016) · Scientific Reports · doi:10.1038/srep23326 · Cited by 31 · see citing works
Defining the proteomic landscape of cultured macrophages and their polarization continuum
Oates, T. C., Moura, P. L., Cross, S., Roberts, K., Baum, H. E., Haydn‐Smith, K. L., Wilson, M. C., Heesom, K. J., Severn, C. E., & Toye, A. M. (2023) · Immunology and Cell Biology · doi:10.1111/imcb.12687 · Cited by 34 · see citing works
CLEC16A—An Emerging Master Regulator of Autoimmunity and Neurodegeneration
Pandey, R., Bakay, M. A., & Hakonarson, H. H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24098224 · Cited by 27 · see citing works
Proust, C., Empana, J. P., Boutouyrie, P., Alivon, M., Challande, P., Danchin, N., Escriou, G., Esslinger, U. B., Laurent, S., Li, Z., et al. (2015) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.114.000979 · Cited by 25 · see citing works
Possible heterogeneity of initial pancreatic islet beta‐cell autoimmunity heralding type 1 diabetes
Lernmark, Å., Akolkar, B., Hagopian, W., Krischer, J. P., McIndoe, R., Rewers, M., Toppari, J., Vehik, K., Ziegler, A., & The TEDDY Study Group (2023) · Journal of Internal Medicine · doi:10.1111/joim.13648 · Cited by 24 · see citing works
Pandey, R., Bakay, M. A., Hain, H. S., Strenkowski, B. P., Yermakova, A., Kushner, J. A., Orange, J. S., & Hakonarson, H. H. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00068 · Cited by 19 · see citing works
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Rijvers, L., Melief, M., van Langelaar, J., de Vries, R. M. V. D. V., Wierenga‐Wolf, A. F., Koetzier, S. C., Priatel, J. J., Jorritsma, T., van Ham, S. M., Hintzen, R. Q., et al. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.1901409 · Cited by 17 · see citing works
Tam, R. C.-Y., Lee, A. L.-H., Yang, W., Lau, C. S., & Chan, V. S. F. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms160714428 · Cited by 10 · see citing works
Exploring the role of the multiple sclerosis susceptibility gene CLEC16A in T cells
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Li, K., Hou, S., Qi, J., Kijlstra, A., & Yang, P. (2015) · Experimental Eye Research · doi:10.1016/j.exer.2015.01.004 · Cited by 5 · see citing works
Sukhija, N., Ganguly, I., Kanaka, K. K., Dixit, S., Singh, S., Bhatia, A. K., Goli, R. C., & Rathi, P. (2025) · Genome · doi:10.1139/gen-2025-0029
- Authors
- Zouk, H., D'Hennezel, E., Du, X., Ounissi-Benkalha, H., Piccirillo, C. A., & Polychronakos, C.
- Affiliations
- Montreal Children's Hospital (CA)
- McGill University Health Centre (CA)
- Endocrine Genetics Laboratory, McGill University Health Center, Montreal Children's Hospital Research Institute, Montreal, QC, Canada
- Corresponding author
- Polychronakos, C
- Venue
- Clinical and Experimental Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-02-04
- Volume
- 175
- Issue
- 3
- Pages
- 485-497
- ISSN
- 0009-9104 (ISSN-L)
- 1365-2249
- PMC
- PMC3927909
- OpenAlex
- W1930060214
- Semantic Scholar
- d1349724f839b75b2b6449d28012313a48f20eb1
- Cited by
- 17
- References
- 45
- Citations by year
- 2025: 1 · 2023: 3 · 2021: 1 · 2020: 2 · 2019: 1 · 2017: 1 · 2016: 2 · 2015: 5 · 2014: 1
- FWCI
- 1.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical & Experimental Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Juvenile Diabetes Research Foundation
- Fonds de Recherche en Santé du Québec
- Montreal Children's Hospital Research Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- CLEC16A, type 1 diabetes, T cell costimulation, antigen-presenting cells, B cells, dendritic cells, T cell activation, T cell proliferation, endoplasmic reticulum localization, subcellular localization, gene knockdown, lymphoblastoid cell lines, autoimmunity
- MeSH terms
- Antigen-Presenting Cells, B-Lymphocytes, Chromosomes, Human, Pair 16, Endoplasmic Reticulum, Humans, Leukocytes, Mononuclear, Lymphocyte Activation, Monosaccharide Transport Proteins, T-Lymphocytes, Coculture Techniques, K562 Cells, Protein Transport, Lectins, C-Type, Gene Knockdown Techniques, Genetic Loci
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