White, Stephen E. and Schwartze, Tristin A. and Mukundan, Ananya and Schoenherr, Christina and Singh, Shashi P. and van Dinther, Maarten and Cunningham, Kyle T. and White, Madeleine P. J. and Campion, Tiffany and Pritchard, John and Hinck, Cynthia S. and ten Dijke, Peter and Inman, Gareth J. and Maizels, Rick M. and Hinck, Andrew P. (2025) TGM6 is a helminth secretory product that mimics TGF-β binding to TGFBR2 to antagonize signaling in fibroblasts. Nature Communications, 16 (1): 1847. ISSN 2041-1723
AI Summary:
TGM6 is a natural antagonist of mammalian TGF- signaling produced by the murine helminth parasite Heligmosomoides polygyrus. It differs from the previously described agonist, TGM1 TGF- Mimic-1, in that it lacks domains 12 that bind TGFBR1.AI Topics:
TGM6 is a natural antagonist of mammalian TGF-β signaling produced by the murine helminth parasite Heligmosomoides polygyrus. It differs from the previously described agonist, TGM1 (TGF-β Mimic-1), in that it lacks domains 1/2 that bind TGFBR1. It nonetheless retains TGFBR2 binding through domain 3 and potently inhibits TGF-β signaling in fibroblasts and epithelial cells, but does not inhibit TGF-β signaling in T cells, consistent with divergent domains 4/5 and an altered co-receptor binding preference. The crystal structure of TGM6 bound to TGFBR2 reveals an interface remarkably similar to that of TGF-β with TGFBR2. Thus, TGM6 has adapted its structure to mimic TGF-β, while engaging a distinct co-receptor to direct antagonism to fibroblasts and epithelial cells. The co-expression of TGM6, along with immunosuppressive TGMs that activate the TGF-β pathway, may minimize fibrotic damage to the host as the parasite progresses through its life cycle from the intestinal lumen to submucosa and back again. The co-receptor-dependent targeting of TGFBR2 by the parasite provides a template for the development of therapies for targeting the cancer- and fibrosis-promoting activities of the TGF-βs in humans.
White, Stephen E.
Author
White, Stephen E. and Schwartze, Tristin A. and Mukundan, Ananya and Schoenherr, Christina and Singh, Shashi P. and van Dinther, Maarten and Cunningham, Kyle T. and White, Madeleine P. J. and Campion, Tiffany and Pritchard, John and Hinck, Cynthia S. and ten Dijke, Peter and Inman, Gareth J. and Maizels, Rick M. and Hinck, Andrew P. (2025) TGM6 is a helminth secretory product that mimics TGF-β binding to TGFBR2 to antagonize signaling in fibroblasts. Nature Communications, 16 (1): 1847. ISSN 2041-1723
See full publications listSchwartze, Tristin A.
Author
White, Stephen E. and Schwartze, Tristin A. and Mukundan, Ananya and Schoenherr, Christina and Singh, Shashi P. and van Dinther, Maarten and Cunningham, Kyle T. and White, Madeleine P. J. and Campion, Tiffany and Pritchard, John and Hinck, Cynthia S. and ten Dijke, Peter and Inman, Gareth J. and Maizels, Rick M. and Hinck, Andrew P. (2025) TGM6 is a helminth secretory product that mimics TGF-β binding to TGFBR2 to antagonize signaling in fibroblasts. Nature Communications, 16 (1): 1847. ISSN 2041-1723
See full publications listMukundan, Ananya
Author
White, Stephen E. and Schwartze, Tristin A. and Mukundan, Ananya and Schoenherr, Christina and Singh, Shashi P. and van Dinther, Maarten and Cunningham, Kyle T. and White, Madeleine P. J. and Campion, Tiffany and Pritchard, John and Hinck, Cynthia S. and ten Dijke, Peter and Inman, Gareth J. and Maizels, Rick M. and Hinck, Andrew P. (2025) TGM6 is a helminth secretory product that mimics TGF-β binding to TGFBR2 to antagonize signaling in fibroblasts. Nature Communications, 16 (1): 1847. ISSN 2041-1723
Singh, Shashi P. and Smyth, Danielle J. and Cunningham, Kyle T. and Mukundan, Ananya and Byeon, Chang-Hyeock and Hinck, Cynthia S. and White, Madeleine P.J. and Ciancia, Claire and Wąsowska, Natalia and Sanders, Anna and Jin, Regina and White, Ruby F. and Lilla, Sergio and Zanivan, Sara and Schoenherr, Christina and Inman, Gareth and van Dinther, Maarten and ten Dijke, Peter and Hinck, Andrew P. and Maizels, Rick M. (2025) The TGF-β mimic TGM4 achieves cell specificity through combinatorial surface co-receptor binding. EMBO Reports, 26 (1). pp. 218-244. ISSN 1469-221X
See full publications listSchoenherr, Christina
Author
White, Stephen E. and Schwartze, Tristin A. and Mukundan, Ananya and Schoenherr, Christina and Singh, Shashi P. and van Dinther, Maarten and Cunningham, Kyle T. and White, Madeleine P. J. and Campion, Tiffany and Pritchard, John and Hinck, Cynthia S. and ten Dijke, Peter and Inman, Gareth J. and Maizels, Rick M. and Hinck, Andrew P. (2025) TGM6 is a helminth secretory product that mimics TGF-β binding to TGFBR2 to antagonize signaling in fibroblasts. Nature Communications, 16 (1): 1847. ISSN 2041-1723
See full publications listSingh, Shashi P.
Author
White, Stephen E. and Schwartze, Tristin A. and Mukundan, Ananya and Schoenherr, Christina and Singh, Shashi P. and van Dinther, Maarten and Cunningham, Kyle T. and White, Madeleine P. J. and Campion, Tiffany and Pritchard, John and Hinck, Cynthia S. and ten Dijke, Peter and Inman, Gareth J. and Maizels, Rick M. and Hinck, Andrew P. (2025) TGM6 is a helminth secretory product that mimics TGF-β binding to TGFBR2 to antagonize signaling in fibroblasts. Nature Communications, 16 (1): 1847. ISSN 2041-1723
Singh, Shashi P. and Smyth, Danielle J. and Cunningham, Kyle T. and Mukundan, Ananya and Byeon, Chang-Hyeock and Hinck, Cynthia S. and White, Madeleine P.J. and Ciancia, Claire and Wąsowska, Natalia and Sanders, Anna and Jin, Regina and White, Ruby F. and Lilla, Sergio and Zanivan, Sara and Schoenherr, Christina and Inman, Gareth and van Dinther, Maarten and ten Dijke, Peter and Hinck, Andrew P. and Maizels, Rick M. (2025) The TGF-β mimic TGM4 achieves cell specificity through combinatorial surface co-receptor binding. EMBO Reports, 26 (1). pp. 218-244. ISSN 1469-221X
See full publications listvan Dinther, Maarten
Author
White, Stephen E. and Schwartze, Tristin A. and Mukundan, Ananya and Schoenherr, Christina and Singh, Shashi P. and van Dinther, Maarten and Cunningham, Kyle T. and White, Madeleine P. J. and Campion, Tiffany and Pritchard, John and Hinck, Cynthia S. and ten Dijke, Peter and Inman, Gareth J. and Maizels, Rick M. and Hinck, Andrew P. (2025) TGM6 is a helminth secretory product that mimics TGF-β binding to TGFBR2 to antagonize signaling in fibroblasts. Nature Communications, 16 (1): 1847. ISSN 2041-1723
Singh, Shashi P. and Smyth, Danielle J. and Cunningham, Kyle T. and Mukundan, Ananya and Byeon, Chang-Hyeock and Hinck, Cynthia S. and White, Madeleine P.J. and Ciancia, Claire and Wąsowska, Natalia and Sanders, Anna and Jin, Regina and White, Ruby F. and Lilla, Sergio and Zanivan, Sara and Schoenherr, Christina and Inman, Gareth and van Dinther, Maarten and ten Dijke, Peter and Hinck, Andrew P. and Maizels, Rick M. (2025) The TGF-β mimic TGM4 achieves cell specificity through combinatorial surface co-receptor binding. EMBO Reports, 26 (1). pp. 218-244. ISSN 1469-221X
See full publications listCunningham, Kyle T.
Author
White, Stephen E. and Schwartze, Tristin A. and Mukundan, Ananya and Schoenherr, Christina and Singh, Shashi P. and van Dinther, Maarten and Cunningham, Kyle T. and White, Madeleine P. J. and Campion, Tiffany and Pritchard, John and Hinck, Cynthia S. and ten Dijke, Peter and Inman, Gareth J. and Maizels, Rick M. and Hinck, Andrew P. (2025) TGM6 is a helminth secretory product that mimics TGF-β binding to TGFBR2 to antagonize signaling in fibroblasts. Nature Communications, 16 (1): 1847. ISSN 2041-1723
Singh, Shashi P. and Smyth, Danielle J. and Cunningham, Kyle T. and Mukundan, Ananya and Byeon, Chang-Hyeock and Hinck, Cynthia S. and White, Madeleine P.J. and Ciancia, Claire and Wąsowska, Natalia and Sanders, Anna and Jin, Regina and White, Ruby F. and Lilla, Sergio and Zanivan, Sara and Schoenherr, Christina and Inman, Gareth and van Dinther, Maarten and ten Dijke, Peter and Hinck, Andrew P. and Maizels, Rick M. (2025) The TGF-β mimic TGM4 achieves cell specificity through combinatorial surface co-receptor binding. EMBO Reports, 26 (1). pp. 218-244. ISSN 1469-221X
See full publications listWhite, Madeleine P.J.
Author
White, Stephen E. and Schwartze, Tristin A. and Mukundan, Ananya and Schoenherr, Christina and Singh, Shashi P. and van Dinther, Maarten and Cunningham, Kyle T. and White, Madeleine P. J. and Campion, Tiffany and Pritchard, John and Hinck, Cynthia S. and ten Dijke, Peter and Inman, Gareth J. and Maizels, Rick M. and Hinck, Andrew P. (2025) TGM6 is a helminth secretory product that mimics TGF-β binding to TGFBR2 to antagonize signaling in fibroblasts. Nature Communications, 16 (1): 1847. ISSN 2041-1723
Singh, Shashi P. and Smyth, Danielle J. and Cunningham, Kyle T. and Mukundan, Ananya and Byeon, Chang-Hyeock and Hinck, Cynthia S. and White, Madeleine P.J. and Ciancia, Claire and Wąsowska, Natalia and Sanders, Anna and Jin, Regina and White, Ruby F. and Lilla, Sergio and Zanivan, Sara and Schoenherr, Christina and Inman, Gareth and van Dinther, Maarten and ten Dijke, Peter and Hinck, Andrew P. and Maizels, Rick M. (2025) The TGF-β mimic TGM4 achieves cell specificity through combinatorial surface co-receptor binding. EMBO Reports, 26 (1). pp. 218-244. ISSN 1469-221X
See full publications listCampion, Tiffany
Author
White, Stephen E. and Schwartze, Tristin A. and Mukundan, Ananya and Schoenherr, Christina and Singh, Shashi P. and van Dinther, Maarten and Cunningham, Kyle T. and White, Madeleine P. J. and Campion, Tiffany and Pritchard, John and Hinck, Cynthia S. and ten Dijke, Peter and Inman, Gareth J. and Maizels, Rick M. and Hinck, Andrew P. (2025) TGM6 is a helminth secretory product that mimics TGF-β binding to TGFBR2 to antagonize signaling in fibroblasts. Nature Communications, 16 (1): 1847. ISSN 2041-1723
See full publications listPritchard, John
Author
White, Stephen E. and Schwartze, Tristin A. and Mukundan, Ananya and Schoenherr, Christina and Singh, Shashi P. and van Dinther, Maarten and Cunningham, Kyle T. and White, Madeleine P. J. and Campion, Tiffany and Pritchard, John and Hinck, Cynthia S. and ten Dijke, Peter and Inman, Gareth J. and Maizels, Rick M. and Hinck, Andrew P. (2025) TGM6 is a helminth secretory product that mimics TGF-β binding to TGFBR2 to antagonize signaling in fibroblasts. Nature Communications, 16 (1): 1847. ISSN 2041-1723
See full publications listHinck, Cynthia S.
Author
White, Stephen E. and Schwartze, Tristin A. and Mukundan, Ananya and Schoenherr, Christina and Singh, Shashi P. and van Dinther, Maarten and Cunningham, Kyle T. and White, Madeleine P. J. and Campion, Tiffany and Pritchard, John and Hinck, Cynthia S. and ten Dijke, Peter and Inman, Gareth J. and Maizels, Rick M. and Hinck, Andrew P. (2025) TGM6 is a helminth secretory product that mimics TGF-β binding to TGFBR2 to antagonize signaling in fibroblasts. Nature Communications, 16 (1): 1847. ISSN 2041-1723
Singh, Shashi P. and Smyth, Danielle J. and Cunningham, Kyle T. and Mukundan, Ananya and Byeon, Chang-Hyeock and Hinck, Cynthia S. and White, Madeleine P.J. and Ciancia, Claire and Wąsowska, Natalia and Sanders, Anna and Jin, Regina and White, Ruby F. and Lilla, Sergio and Zanivan, Sara and Schoenherr, Christina and Inman, Gareth and van Dinther, Maarten and ten Dijke, Peter and Hinck, Andrew P. and Maizels, Rick M. (2025) The TGF-β mimic TGM4 achieves cell specificity through combinatorial surface co-receptor binding. EMBO Reports, 26 (1). pp. 218-244. ISSN 1469-221X
See full publications listten Dijke, Peter
Author
White, Stephen E. and Schwartze, Tristin A. and Mukundan, Ananya and Schoenherr, Christina and Singh, Shashi P. and van Dinther, Maarten and Cunningham, Kyle T. and White, Madeleine P. J. and Campion, Tiffany and Pritchard, John and Hinck, Cynthia S. and ten Dijke, Peter and Inman, Gareth J. and Maizels, Rick M. and Hinck, Andrew P. (2025) TGM6 is a helminth secretory product that mimics TGF-β binding to TGFBR2 to antagonize signaling in fibroblasts. Nature Communications, 16 (1): 1847. ISSN 2041-1723
Singh, Shashi P. and Smyth, Danielle J. and Cunningham, Kyle T. and Mukundan, Ananya and Byeon, Chang-Hyeock and Hinck, Cynthia S. and White, Madeleine P.J. and Ciancia, Claire and Wąsowska, Natalia and Sanders, Anna and Jin, Regina and White, Ruby F. and Lilla, Sergio and Zanivan, Sara and Schoenherr, Christina and Inman, Gareth and van Dinther, Maarten and ten Dijke, Peter and Hinck, Andrew P. and Maizels, Rick M. (2025) The TGF-β mimic TGM4 achieves cell specificity through combinatorial surface co-receptor binding. EMBO Reports, 26 (1). pp. 218-244. ISSN 1469-221X
See full publications listInman, Gareth
Author
White, Stephen E. and Schwartze, Tristin A. and Mukundan, Ananya and Schoenherr, Christina and Singh, Shashi P. and van Dinther, Maarten and Cunningham, Kyle T. and White, Madeleine P. J. and Campion, Tiffany and Pritchard, John and Hinck, Cynthia S. and ten Dijke, Peter and Inman, Gareth J. and Maizels, Rick M. and Hinck, Andrew P. (2025) TGM6 is a helminth secretory product that mimics TGF-β binding to TGFBR2 to antagonize signaling in fibroblasts. Nature Communications, 16 (1): 1847. ISSN 2041-1723
Singh, Shashi P. and Smyth, Danielle J. and Cunningham, Kyle T. and Mukundan, Ananya and Byeon, Chang-Hyeock and Hinck, Cynthia S. and White, Madeleine P.J. and Ciancia, Claire and Wąsowska, Natalia and Sanders, Anna and Jin, Regina and White, Ruby F. and Lilla, Sergio and Zanivan, Sara and Schoenherr, Christina and Inman, Gareth and van Dinther, Maarten and ten Dijke, Peter and Hinck, Andrew P. and Maizels, Rick M. (2025) The TGF-β mimic TGM4 achieves cell specificity through combinatorial surface co-receptor binding. EMBO Reports, 26 (1). pp. 218-244. ISSN 1469-221X
Smith, Craig D.L. and McMahon, Alex D. and Purkayastha, Mitana and Creaney, Grant and Clements, Kelten and Inman, Gareth J. and Bhatti, Lesley A. and Douglas, Catriona M. and Paterson, Claire and Conway, David I. (2024) Head and neck cancer incidence is rising but the sociodemographic profile is unchanging: a population epidemiological study (2001-2020). BJC Reports, 2: 71. ISSN 2731-9377
See full publications listMaizels, Rick M.
Author
White, Stephen E. and Schwartze, Tristin A. and Mukundan, Ananya and Schoenherr, Christina and Singh, Shashi P. and van Dinther, Maarten and Cunningham, Kyle T. and White, Madeleine P. J. and Campion, Tiffany and Pritchard, John and Hinck, Cynthia S. and ten Dijke, Peter and Inman, Gareth J. and Maizels, Rick M. and Hinck, Andrew P. (2025) TGM6 is a helminth secretory product that mimics TGF-β binding to TGFBR2 to antagonize signaling in fibroblasts. Nature Communications, 16 (1): 1847. ISSN 2041-1723
Singh, Shashi P. and Smyth, Danielle J. and Cunningham, Kyle T. and Mukundan, Ananya and Byeon, Chang-Hyeock and Hinck, Cynthia S. and White, Madeleine P.J. and Ciancia, Claire and Wąsowska, Natalia and Sanders, Anna and Jin, Regina and White, Ruby F. and Lilla, Sergio and Zanivan, Sara and Schoenherr, Christina and Inman, Gareth and van Dinther, Maarten and ten Dijke, Peter and Hinck, Andrew P. and Maizels, Rick M. (2025) The TGF-β mimic TGM4 achieves cell specificity through combinatorial surface co-receptor binding. EMBO Reports, 26 (1). pp. 218-244. ISSN 1469-221X
See full publications listHinck, Andrew P.
Author
White, Stephen E. and Schwartze, Tristin A. and Mukundan, Ananya and Schoenherr, Christina and Singh, Shashi P. and van Dinther, Maarten and Cunningham, Kyle T. and White, Madeleine P. J. and Campion, Tiffany and Pritchard, John and Hinck, Cynthia S. and ten Dijke, Peter and Inman, Gareth J. and Maizels, Rick M. and Hinck, Andrew P. (2025) TGM6 is a helminth secretory product that mimics TGF-β binding to TGFBR2 to antagonize signaling in fibroblasts. Nature Communications, 16 (1): 1847. ISSN 2041-1723
See full publications listAvailable under License Creative Commons Attribution.
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