Publications on the TGM (Transforming Growth Factor-β Mimic) protein family from the helminth Heligmosomoides polygyrus. Updated 02.07.2024
Gene Identification, Evolution and Multi-gene Family
Johnston, C.J.C., Smyth, D.J., Kodali, R.B., White, M.P.J., Harcus, Y., Filbey, K.J., Hewitson, J.P., Hinck, C.S., Ivens, A., Kemter, A.M., Kildemoes, A.O., Le Bihan, T., Soares, D., Anderton, S.M., Brenn, T., Wigmore, S.J., Woodcock, H., Chambers, R.C., Hinck, A.P., McSorley, H.J. and Maizels, R.M. (2017) A structurally distinct TGF-β mimic from an intestinal helminth parasite potently induces regulatory T cells. Nature Communications8:1741. PMCID 5701006.
https://www.ncbi.nlm.nih.gov/pubmed/29170498
Smyth, D.J., Harcus, Y., White, M.P.J., Gregory, W.F., Nahler, J., Stephens, I., Toke-Bjolgerud, E., Hewitson, J.P., Ivens, A., McSorley, H.J. and Maizels, R.M. (2018) TGF-β mimic proteins form an extended gene family in the murine parasite Heligmosomoides polygyrus. International Journal of Parasitology 48: 379-385. PMCID 5904571
https://www.ncbi.nlm.nih.gov/pubmed/29510118
Maizels, R.M. and Newfeld, S. (2023) Convergent evolution in a murine intestinal parasite rapidly created the TGM family of molecular mimics to suppress the host immune response. Genome Biology and Evolution 15:evad158. doi: 10.1093/gbe/evad158. PMCID 10516467
https://www.ncbi.nlm.nih.gov/pubmed/37625791
Induction of Regulatory T Cells
Cook, L., Reid, K.T., Häkkinen, E., de Bie, B., Tanaka, S., Smyth, D.J., White, M.P.J., Wong, M.Q., Huang, Q., Gillies, J.K., Ziegler, S.F., Maizels, R.M. and Levings, M.K. (2021) Induction of stable human FOXP3+ T regs by a parasite-derived TGFβ mimic. Immunology and Cell Biology, 99: 833-847. PMCID 8453874
https://www.ncbi.nlm.nih.gov/pubmed/33929751
White, M.P.J., Smyth, D.J., Cook, L., Ziegler, S.F., Levings, M. and Maizels, R.M. (2021) The parasite cytokine mimic Hp-TGM potently replicates the regulatory effects of TGF-β on murine T cells. Immunology and Cell Biology 99: 848-864
PMCID 9214624
https://www.ncbi.nlm.nih.gov/pubmed/33988885
Structural Biology and Biochemistry
Mukundan, A., Byeon, C.-H., Hinck C.S., Cunningham, K., Campion, T., Smyth, D.J., Maizels, R.M. and Hinck, A.P. (2022) Convergent evolution of a parasite-encoded complement control protein-scaffold to mimic binding of mammalian TGF-β to its receptors, TβRI and TβRII. Journal of Biological Chemistry 298:101994. doi 10.1016/j.jbc.2022.101994 PMCID 9163516
https://www.ncbi.nlm.nih.gov/pubmed/35500648
van Dinther, M., Singh, S., Cunningham, K., White, M.P.J., Campion, T., Ciancia, C., van Veelem. P.A., de Ru, A.H., Gonzalez-Prieto, R., Mukundan, A., Byeon, C.-H., Staggers, S.R., Hinck, C.S., Hinck, A.P., ten Dijke, P, and Maizels, R.M. (2023) CD44 acts as a co-receptor for cell-specific enhancement of signaling and regulatory T cell induction by TGM1, a parasite TGF-β mimic. Proc Natl Acad Sci USA 120: e2302370120. doi 10.1073/pnas. 2302370120. PMCID 10450677
https://www.ncbi.nlm.nih.gov/pubmed/37590410
Singh, S.P., Smyth, D.J., Cunningham, K., Mukundan, A., Byeon, C.-H., Hinck, C.S., White, M.P.J., Ciancia, C., Wosowska, N., Sanders, A., Jin, R., Lilla, S., Zanivan, S., Schoenherr, C., Inman, G., Dinther, M., ten Dijke, P., Hinck, A.P. and Maizels, R.M. (2024). The helminth TGF-β mimic TGM4 is a modular ligand that binds CD44, CD49d and TGF-β receptors to preferentially target myeloid cells. EMBO Reports, under revision, available on BioRχiv 2023.11.13.566701
https://doi.org/10.1101/2023.11.13.566701
White, S.E., Schwartze, T.A., Mukundan, A., Schoenherr, C., Singh, S.P., van Dinther, M., Cunningham, K., White, M.P.J., Campion, T., Pritchard, J., Hinck, C.S., ten Dijke, P., Inman, G., Maizels, R.M. and Hinck, A.P. (2024). TGM6, a helminth secretory product, mimics TGF-β binding to TβRII to antagonize TGF-β signaling in fibroblasts.Nature Communications, under revision; available on BioRχiv 2023.12.22.573140
https://doi.org/10.1101/2023.12.22.573140
Suppression of Inflammation in vivo
Smyth, D.J., Ren, B., White, M., McManus, C., Webster, H., Shek, V., Evans, C., Pandhal, J., Fields, F., Maizels, R.M. and Mayfield, S. (2021). Oral delivery of a functional algal-expressed TGF-β mimic halts colitis in a murine DSS model. Journal of Biotechnology 340 : 1-12 PMCID 8516079
https://www.ncbi.nlm.nih.gov/pubmed/34390759
Chauché, C., Rasid, O., Donachie, A.-M., McManus, C.M., Loeser, S., Richards, J., Campion, T., Smyth, D.J., McSorley, H.J. and Maizels, R.M. (2022) Suppression of airway allergic eosinophilia by Hp-TGM-1, a helminth mimic of TGF-β. Immunology 167: 197-211; doi 10.1111/imm.13528. PMCID 9885513
https://www.ncbi.nlm.nih.gov/pubmed/35758054
Redgrave, R.E., Singh, E., Tual-Chalot, S., Park, C., Hall, D., Bennaceur, K., Smyth, D.J., Maizels, R.M., Spyridopoulos, I. and Arthur, H.M. (2023). Exogenous transforming growth factor-β and its mimicHeligmosomoides polygyrus TGM attenuate the heart’s inflammatory response to ischemic injury and reduce mature scar size American Journal of Pathology, 194: 562-573 doi 10.1016/j.ajpath.2023.09.014
https://www.ncbi.nlm.nih.gov/pubmed/37832870
Smyth, D.J., White, M.P.J., Johnston, C.J.C., Donachie, A.-M., Campillo Poveda, M, McSorley, H.J. and Maizels, R.M. (2023) Protection from T cell-dependent colitis by the helminth-derived immunomodulatory mimic of transforming growth factor-β, TGM. Discovery Immunology 2: 1-12. doi: 10.1093/discim/kyad001. PMCID 9958376
https://www.ncbi.nlm.nih.gov/pubmed/36855464
Lothstein, K.E., Chen, F., Mishra, P., Smyth, D.J., Wu, W., Lemenze, A., Kumamoto, Y., Maizels, R.M. and Gause, W.C. (2024). A helminth mimic of TGF-β, TGM, enhances regenerative cutaneous wound healing and modulates immune cell recruitment and activation. BioRχiv 2022.09.24.509317;
https://doi.org/10.1101/2022.09.24.509317