dc.creator | van Dinther, Maarten | es |
dc.creator | Cunningham, Kyle T. | es |
dc.creator | Singh, Shashi Prakash | es |
dc.creator | White, Madeleine P.J. | es |
dc.creator | Campion, Tiffany | es |
dc.creator | Ciancia, Claire | es |
dc.creator | van Veelen, Peter A. | es |
dc.creator | de Ru, Arnoud H. | es |
dc.creator | González Prieto, Román | es |
dc.creator | Mukundan, Ananya | es |
dc.creator | Maizels, Rick M. | es |
dc.date.accessioned | 2024-02-14T15:02:36Z | |
dc.date.available | 2024-02-14T15:02:36Z | |
dc.date.issued | 2023 | |
dc.identifier.citation | van Dinther, M., Cunningham, K.T., Singh, S.P., White, M.P.J., Campion, T., Ciancia, C.,...,Maizels, R.M. (2023). CD44 Acts as a Coreceptor for Cell-specific Enhancement of Signaling and Regulatory T Cell Induction by TGM1, a Parasite TGF-β Mimic. Proceedings of the National Academy of Sciences of the United States of America, 120 (34), e2302370120. https://doi.org/10.1073/pnas.2302370120. | |
dc.identifier.issn | 0027-8424 | es |
dc.identifier.issn | 1091-6490 | es |
dc.identifier.uri | https://hdl.handle.net/11441/155242 | |
dc.description.abstract | Long-lived parasites evade host immunity through highly evolved molecular strategies. The murine intestinal helminth, Heligmosomoides polygyrus, down-modulates the host immune system through release of an immunosuppressive TGF-β mimic, TGM1, which is a divergent member of the CCP (Sushi) protein family. TGM1 comprises 5 domains, of which domains 1-3 (D1/2/3) bind mammalian TGF-β receptors, acting on T cells to induce Foxp3+ regulatory T cells; however, the roles of domains 4 and 5 (D4/5) remain unknown. We noted that truncated TGM1, lacking D4/5, showed reduced potency. Combination of D1/2/3 and D4/5 as separate proteins did not alter potency, suggesting that a physical linkage is required and that these domains do not deliver an independent signal. Coprecipitation from cells treated with biotinylated D4/5, followed by mass spectrometry, identified the cell surface protein CD44 as a coreceptor for TGM1. Both full-length and D4/5 bound strongly to a range of primary cells and cell lines, to a greater degree than D1/2/3 alone, although some cell lines did not respond to TGM1. Ectopic expression of CD44 in nonresponding cells conferred responsiveness, while genetic depletion of CD44 abolished enhancement by D4/5 and ablated the ability of full-length TGM1 to bind to cell surfaces. Moreover, CD44-deficient T cells showed attenuated induction of Foxp3 by full-length TGM1, to levels similar to those induced by D1/2/3. Hence, a parasite protein known to bind two host cytokine receptor subunits has evolved a third receptor specificity, which serves to raise the avidity and cell type–specific potency of TGF-β signaling in mammalian cells. | es |
dc.description.sponsorship | Wellcome Trust 219530 | es |
dc.description.sponsorship | Wellcome Centre for Integrative Parasitology 10411 | es |
dc.description.sponsorship | National Institutes of Health AI153915, AI57069 | es |
dc.format | application/pdf | es |
dc.format.extent | 12 p. | es |
dc.language.iso | eng | es |
dc.publisher | National Academy of Sciences | es |
dc.relation.ispartof | Proceedings of the National Academy of Sciences of the United States of America, 120 (34), e2302370120. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Complement control protein | es |
dc.subject | Convergent evolution | es |
dc.subject | Fibroblast | es |
dc.subject | Heligmosomoides polygyrus | es |
dc.subject | T lymphocyte | es |
dc.title | CD44 Acts as a Coreceptor for Cell-specific Enhancement of Signaling and Regulatory T Cell Induction by TGM1, a Parasite TGF-β Mimic | es |
dc.type | info:eu-repo/semantics/article | es |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Biología Celular | es |
dc.relation.projectID | 219530 | es |
dc.relation.projectID | 10411 | es |
dc.relation.projectID | AI153915 | es |
dc.relation.projectID | AI57069 | es |
dc.relation.publisherversion | https://dx.doi.org/10.1073/pnas.2302370120 | es |
dc.identifier.doi | 10.1073/pnas.2302370120 | es |
dc.journaltitle | Proceedings of the National Academy of Sciences of the United States of America | es |
dc.publication.volumen | 120 | es |
dc.publication.issue | 34 | es |
dc.publication.initialPage | e2302370120 | es |
dc.contributor.funder | Wellcome Trust. Reino Unido. | es |
dc.contributor.funder | Wellcome Centre for Integrative Parasitology. Reino Unido. | es |
dc.contributor.funder | National Institutes of Health (NIH). EE.UU. | es |