Article

Transforming Growth Factor-β Regulation of Immune Responses

Yale University, New Haven, Connecticut, United States
Annual Review of Immunology (Impact Factor: 39.33). 02/2006; 24(1):99-146. DOI: 10.1146/annurev.immunol.24.021605.090737
Source: PubMed

ABSTRACT

Transforming growth factor-beta (TGF-beta) is a potent regulatory cytokine with diverse effects on hemopoietic cells. The pivotal function of TGF-beta in the immune system is to maintain tolerance via the regulation of lymphocyte proliferation, differentiation, and survival. In addition, TGF-beta controls the initiation and resolution of inflammatory responses through the regulation of chemotaxis, activation, and survival of lymphocytes, natural killer cells, dendritic cells, macrophages, mast cells, and granulocytes. The regulatory activity of TGF-beta is modulated by the cell differentiation state and by the presence of inflammatory cytokines and costimulatory molecules. Collectively, TGF-beta inhibits the development of immunopathology to self or nonharmful antigens without compromising immune responses to pathogens. This review highlights the findings that have advanced our understanding of TGF-beta in the immune system and in disease.

Download full-text

Full-text

Available from: Richard A Flavell
  • Source
    • "Deficiency in either the cytokine or its receptors results in fulminant inflammatory disease that proves lethal in the first weeks of life [27], a phenotype that can be reproduced even if only T cells are unable to respond to TGF-b [28]. The cytokine is instrumental in almost every compartment of the immune system [29], inducing for example B cell class switching to IgA [30] [31] and driving myeloid cells into a more tumor-promoting phenotype [32]. But its effects on T cells are perhaps the most prominent, in particular its ability to stimulate naïve CD4 + T cells to differentiate into Foxp3 + Treg that can suppress effector T cell activation and proliferation [33] [34], and prolong allograft survival upon adoptive transfer into recipient animals [35]. "

    Full-text · Dataset · Jan 2016
  • Source
    • "Deficiency in either the cytokine or its receptors results in fulminant inflammatory disease that proves lethal in the first weeks of life [27], a phenotype that can be reproduced even if only T cells are unable to respond to TGF-b [28]. The cytokine is instrumental in almost every compartment of the immune system [29], inducing for example B cell class switching to IgA [30] [31] and driving myeloid cells into a more tumor-promoting phenotype [32]. But its effects on T cells are perhaps the most prominent, in particular its ability to stimulate naïve CD4 + T cells to differentiate into Foxp3 + Treg that can suppress effector T cell activation and proliferation [33] [34], and prolong allograft survival upon adoptive transfer into recipient animals [35]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The TGF-β superfamily is an ancient metazoan protein class which cuts across cell and tissue differentiation, developmental biology and immunology. Its many members are regulated at multiple levels from intricate control of gene transcription, post-translational processing and activation, and signaling through overlapping receptor structures and downstream intracellular messengers. We have been interested in TGF-β homologues firstly as key players in the induction of immunological tolerance, the topic so closely associated with Ray Owen. Secondly, our interests in how parasites may manipulate the immune system of their host has also brought us to study the TGF-β pathway in infections with longlived, essentially tolerogenic, helminth parasites. Finally, within the spectrum of mammalian TGF-β proteins is an exquisitely tightly-regulated gene, anti-Müllerian hormone (AMH), whose role in sex determination underpins the phenotype of freemartin calves that formed the focus of Ray's seminal work on immunological tolerance.
    Full-text · Article · Nov 2015 · Cellular Immunology
  • Source
    • "Transforming growth factor TGF-β belongs to a family of regulatory cytokines that have pleiotropic functions in a broad range of cell lineages involved in numerous physiological and pathological processes such as embryogenesis, carcinogenesis, and the immune responses (Blobe et al., 2000; Wharton and Derynck , 2009; Li et al., 2006). TGF-βs are the prototype of the TGF-β superfamily (Massagué, 1990). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Transforming growth factor (TGF-β) is a well-known component of a regulatory cytokines superfamily that has pleiotropic functions in a broad range of cell types and is involved, in vertebrates, in numerous physiological and pathological processes. In the current study, we report on Ciona intestinalis molecular characterisation and expression of a transforming growth factor β homologue (CiTGF-β). The gene organisation, phylogenetic tree and modelling supported the close relationship with the mammalian TGF suggesting that the C. intestinalis TGF-β gene shares a common ancestor in the chordate lineages. Functionally, real-time PCR analysis showed that CiTGF-β was transcriptionally upregulated in the inflammatory process induced by LPS inoculation, suggesting that is involved in the first phase and significant in the secondary phase of the inflammatory response in which cell differentiation occurs. In situ hybridisation assays revealed that the genes transcription was upregulated in the pharynx, the main organ of the ascidian immune system, and expressed by cluster of hemocytes inside the pharynx vessels. These data supported the view that CiTGF-β is a potential molecule in immune defence systems against bacterial infection.
    Full-text · Article · Oct 2015 · Developmental and comparative immunology
Show more