Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

Sanjabi, Shomyseh; Oh, Soyoung; Li, Ming O.

doi:10.1101/cshperspect.a022236

Cited by 478 publications

(344 citation statements)

References 381 publications

(358 reference statements)

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“…Immunosuppressive roles of GARP through the regulation of TGF-β As described in the earlier section, TGF-β regulates the differentiation and function of multiple types of immune cells, which in turn inhibits immune responses [56]. Among them, TGF-β plays a central role in conversion of naïve T cells into Tregs.…”

Section: Garp Anchors the Latent Tgf-β Complex On The Cell Surfacementioning

confidence: 96%

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Intracellular and extracellular TGF-β signaling in cancer: some recent topics

et al. 2018

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Transforming growth factor (TGF)-β regulates a wide variety of cellular responses, including cell growth arrest, apoptosis, cell differentiation, motility, invasion, extracellular matrix production, tissue fibrosis, angiogenesis, and immune function. Although tumor-suppressive roles of TGF-β have been extensively studied and well-characterized in many cancers, especially at early stages, accumulating evidence has revealed the critical roles of TGF-β as a pro-tumorigenic factor in various types of cancer. This review will focus on recent findings regarding epithelial-mesenchymal transition (EMT) induced by TGF-β, in relation to crosstalk with some other signaling pathways, and the roles of TGF-β in lung and pancreatic cancers, in which TGF-β has been shown to be involved in cancer progression. Recent findings also strongly suggested that targeting TGF-β signaling using specific inhibitors may be useful for the treatment of some cancers. TGF-β plays a pivotal role in the differentiation and function of regulatory T cells (Tregs). TGF-β is produced as latent high molecular weight complexes, and the latent TGF-β complex expressed on the surface of Tregs contains glycoprotein A repetitions predominant (GARP, also known as leucine-rich repeat containing 32 or LRRC32). Inhibition of the TGF-β activities through regulation of the latent TGF-β complex activation will be discussed.

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Section: Garp Anchors the Latent Tgf-β Complex On The Cell Surfacementioning

confidence: 96%

“…TGF-β functions as a potent immunosuppressive cytokine [53][54][55][56] and therefore, inhibition of TGF-β signaling in the immune system may lead to an enhancement of tumor immunity. TGF-β suppresses the proliferation of T and B cells and the functions of cytotoxic CD8 + T cells and helper CD4…”

Section: Immune Responsesmentioning

confidence: 99%

Intracellular and extracellular TGF-β signaling in cancer: some recent topics

et al. 2018

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“…Transforming growth factor type‐ β (TGF‐β) has many biological activities, and is thought to be a particularly important contributor to fibrosis, angiogenesis, and tissue repair. In addition, TGF‐β can influence T cells, including Th17 and Treg cells (reviewed in), as well as B cells, dendritic cells, NK cells, neutrophils, eosinophils, and MCs (reviewed in ).…”

Section: Mast Cell‐derived Cytokines Growth Factors and Mitogensmentioning

confidence: 99%

Mast cells as sources of cytokines, chemokines, and growth factors

Mukai

Tsai

Saito

et al. 2018

Immunological Reviews

553

508

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Mast cells are hematopoietic cells that reside in virtually all vascularized tissues and that represent potential sources of a wide variety of biologically active secreted products, including diverse cytokines and growth factors. There is strong evidence for important non-redundant roles of mast cells in many types of innate or adaptive immune responses, including making important contributions to immediate and chronic IgE-associated allergic disorders and enhancing host resistance to certain venoms and parasites. However, mast cells have been proposed to influence many other biological processes, including responses to bacteria and virus, angiogenesis, wound healing, fibrosis, autoimmune and metabolic disorders, and cancer. The potential functions of mast cells in many of these settings is thought to reflect their ability to secrete, upon appropriate activation by a range of immune or non-immune stimuli, a broad spectrum of cytokines (including many chemokines) and growth factors, with potential autocrine, paracrine, local, and systemic effects. In this review, we summarize the evidence indicating which cytokines and growth factors can be produced by various populations of rodent and human mast cells in response to particular immune or non-immune stimuli, and comment on the proven or potential roles of such mast cell products in health and disease.

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“…Immunotherapy based on checkpoint inhibitors and chimeric antigen receptor (CAR) T cells represents a breakthrough in cancer therapy [77]. Mounting evidence indicates that TGF-β is a potent immunosuppressive cytokine involved in suppressive immune responses [9,[78][79][80]. In addition, it has been reported that high levels of TGF-β are frequently found in colorectal carcinomas, which are clinically associated with poor survival in patients [81,82].…”

Section: Rewiring Of Tgf-β Signaling Toward Clinical Applicationsmentioning

confidence: 99%

Molecular Engineering of the TGF-β Signaling Pathway

2019

Journal of Molecular Biology

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Transforming growth factor beta (TGF-β) is an important growth factor that plays essential roles in regulating tissue development and homeostasis. Dysfunction of TGF-β signaling is a hallmark of many human diseases. Therefore, targeting TGF-β signaling presents broad therapeutic potential. Since the discovery of the TGF-β ligand, a collection of engineered signaling proteins have been developed to probe and manipulate TGF-β signaling responses. In this review, we highlight recent progress in the engineering of TGF-β signaling for different applications and discuss how molecular engineering approaches can advance our understanding of this important pathway. In addition, we provide a future outlook on the opportunities and challenges in the engineering of the TGF-β signaling pathway from a quantitative perspective.

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Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

Cited by 478 publications

References 381 publications

Intracellular and extracellular TGF-β signaling in cancer: some recent topics

Intracellular and extracellular TGF-β signaling in cancer: some recent topics

Mast cells as sources of cytokines, chemokines, and growth factors

Molecular Engineering of the TGF-β Signaling Pathway

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