ArticleInternational journal for parasitology2018
TGF-β mimic proteins form an extended gene family in the murine parasite Heligmosomoides polygyrus.
Article in International journal for parasitology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 61 citations in OpenAlex.
- Curtailment of Toll-like receptor signalling and cytokine production in dendritic cells by secreted products of Heligmosomoides polygyrus.PLoS pathogens · 2026Article
- Decoding the Mechanism of Action of a Parasite TGFβ Antagonist Inspires the Creation of Cell-Type-Specific TGFβ Modulators.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- In vivo reduction of Treg expansion in rodent helminth-malaria coinfection.Parasites & vectors · 2026Article
- Molecular Engineering of the Helminth TGF-β Mimetics, TGM1 and TGM4, Reveals a Novel Antagonist of TGF-β Signaling in Fibroblasts.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- The dual role of intestinal parasites in shaping human gut microbiota: distinguishing helminthic and protozoan dynamics.Gut pathogens · 2026Review
- Structural and functional analysis of the TGF-β mimic, TGM-2: an immunomodulatory helminth protein.Genes and immunity · 2026Article
- Vaccination against helminth IL-33 modulators permits immune-mediated parasite ejection.Cell reports · 2025Article
- Cytokines from parasites: manipulating host responses by molecular mimicry.The Biochemical journal · 2025Review
- TGM6 is a helminth secretory product that mimics TGF-β binding to TGFBR2 to antagonize signaling in fibroblasts.Nature communications · 2025Article
- Article
- Helminth protein enhances wound healing by inhibiting fibrosis and promoting tissue regeneration.Life science alliance · 2024Article
- 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 · 2023Review
- 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 · 2023Article
- Transcriptional patterns of sexual dimorphism and in host developmental programs in the model parasitic nematode Heligmosomoides bakeri.Parasites & vectors · 2023Article
- Protection from T cell-dependent colitis by the helminth-derived immunomodulatory mimic of transforming growth factor-β,Discovery immunology · 2023Article
- Importance of TGFβ in Cancer and Nematode Infection and Their Interaction-Opinion.Biomolecules · 2022Review
- Article
- A filarial parasite-encoded human IL-10 receptor antagonist reveals a novel strategy to modulate host responses.PNAS nexus · 2022Article
- Convergent evolution of a parasite-encoded complement control protein-scaffold to mimic binding of mammalian TGF-β to its receptors, TβRI and TβRII.The Journal of biological chemistry · 2022Article
- The evolution of powerful yet perilous immune systems.Trends in immunology · 2022Review
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
Abstract
We recently reported the discovery of a new parasite-derived protein that functionally mimics the immunosuppressive cytokine transforming growth factor (TGF)-β. The Heligmosomoides polygyrus TGF-β Mimic (Hp-TGM) shares no homology to any TGF-β family member, however it binds the mammalian TGF-β receptor and induces expression of Foxp3, the canonical transcription factor of both mouse and human regulatory T cells. Hp-TGM consists of five atypical Complement Control Protein (CCP, Pfam 00084) domains, each lacking certain conserved residues and 12-15 amino acids longer than the 60-70 amino acids consensus domain, but with a recognizable 3-cysteine, tryptophan, cysteine motif. We now report on the identification of a family of nine related Hp-TGM homologues represented in the secreted proteome and transcriptome of H. polygyrus. Recombinant proteins from five of the nine new TGM members were tested for TGF-β activity, but only two were functionally active in an MFB-F11 reporter assay, and by the induction of T cell Foxp3 expression. Sequence comparisons reveal that proteins with functional activity are similar or identical to Hp-TGM across the first three CCP domains, but more variable in domains 4 and 5. Inactive proteins diverged in all domains, or lacked some domains entirely. Testing truncated versions of Hp-TGM confirmed that domains 1-3 are essential for full activity in vitro, while domains 4 and 5 are not required. Further studies will elucidate whether these latter domains fulfill other functions in promoting host immune regulation during infection and if the more divergent family members play other roles in immunomodulation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.