Revisiting the regulatory roles of the TGF-β family of cytokines

Fujio, K.; Komai, Takashi; Inoue, Mariko; Morita, Kaoru; Okamura, Tomohisa; Yamamoto, Kauzhiko

doi:10.1016/j.autrev.2016.07.007

Cited by 91 publications

(73 citation statements)

References 61 publications

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“…TGF-β2, however, is thought to play an insignificant role in the immune system due to its low expression in immune cells [8]. Recent accumulating evidence on the expression and function of TGF-β3 in immunity has revealed similarities and differences between TGF-β1 and TGF-β3 [9,10]. In this review, we focus on the molecular characteristics, immunological roles, and future possibilities of TGF-β3 in comparison to TGF-β1.…”

Section: Introductionmentioning

confidence: 99%

Reevaluation of Pluripotent Cytokine TGF-β3 in Immunity

Komai

Okamura

Inoue

et al. 2018

IJMS

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Transforming growth factor (TGF)-βs are pluripotent cytokines with stimulatory and inhibitory properties for multiple types of immune cells. Analyses of genetic knockouts of each isoform of TGF-β have revealed differing expression patterns and distinct roles for the three mammalian isoforms of TGF-β. Considerable effort has been focused on understanding the molecular mechanisms of TGF-β1-mediated immune regulation, given its pivotal role in prohibiting systemic autoimmune disease. In recent years, functional similarities and differences between the TGF-β isoforms have delineated their distinct roles in the development of immunopathology and immune tolerance, with increased recent attention being focused on TGF-β3. In addition to the characteristic properties of each TGF-β isoform, recent progress has identified determinants of context-dependent functionality, including various cellular targets, cytokine concentrations, tissue microenvironments, and cytokine synergy, which combine to shape the physiological and pathophysiological roles of the TGF-βs in immunity. Controlling TGF-β production and signaling is being tested as a novel therapeutic strategy in multiple clinical trials for several human diseases. This review highlights advances in the understanding of the cellular sources, activation processes, contextual determinants, and immunological roles of TGF-β3 with comparisons to other TGF-β isoforms.

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Section: Introductionmentioning

confidence: 99%

Reevaluation of Pluripotent Cytokine TGF-β3 in Immunity

Komai

Okamura

Inoue

et al. 2018

IJMS

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“…Furthermore, proteins present on the ECM, e.g. fibrin, fibronectin, and thrombospondin, can also activate or prevent the function of TGF-β1 by mechanisms not yet completely defined [11,14].…”

Section: Expression and Activation Of Tgf-β1mentioning

confidence: 99%

“…Among them, Smad1, Smad2, Smad3, Smad5, and Smad8 are R-Smads; Smad4 is Co-Smad, and Smad 6 and Smad7 are I-Smads [18]. Generally, Smad2 and Smad3 are R-Smads activated by TGF-β1 [14] once they are phosphorylated by activated TβRI [11]. Phosphorylated R-Smads then interact with Smad4 and translocate into the nucleus where they interact with transcription factors and initiate the transcription of TGF-β1 target genes [8,9,21].…”

Section: Smad-dependent Signaling Pathwaymentioning

confidence: 99%

“…TGF-β1 is fundamental to the regulation of T and B cells [11,12]. Helper T (Th) cells expressing CD4 are differentiated into different Th cell subsets including Th1, Th2, Th17, and Treg depending on the complex interaction between the DCpresenting antigens and cytokines participating in the activation process.…”

Section: T and B Cellsmentioning

confidence: 99%

“…Since its first purification at the beginning of the 1980s, studies have reported the role of TGF-β1 in the regulation of development, as well as in the immune system, tissue regeneration and even the progression of various diseases [10]. The immune regulatory functions of TGF-β1 have been studied extensively in the adaptive immune system since it was first found to be a master regulator of T cell tolerance; it regulates the proliferation, differentiation, and cellular activities of T cell subsets [11,12]. On the other hand, few studies have examined the role of TGF-β1 in regulating the innate immune system, particularly against respiratory bacterial infections.…”

Section: Introductionmentioning

confidence: 99%

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Role of the transforming growth factor (TGF)-β1 and TGF-β1 signaling pathway on the pathophysiology of respiratory pneumococcal infections

Andrade

Lim

2017

Yeungnam Univ J Med

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Streptococcus pneumoniae, pneumococcus, is the most common cause of community-acquired pneumonia (CAP). CAP is an important infectious disease with high morbidity and mortality, and it is still one of the leading causes of death worldwide. Many genetic factors of the host and various environmental factors surrounding it have been studied as important determinants of the pathophysiology and outcomes of pneumococcal infections. Various cytokines, including transforming growth factor (TGF)-β1, are involved in different stages of the progression of pneumococcal infection. TGF-β1 is a cytokine that regulates a wide range of cellular and physiological functions, including immune and inflammatory responses. This cytokine has long been known as an anti-inflammatory cytokine that is critical to preventing the progression of an acute infection to a chronic condition. On the other hand, recent studies have unveiled the diverse roles of TGF-β1 on different stages of pneumococcal infections other than mitigating inflammation. This review summarizes the recent findings of the role of TGF-β1 on the pathophysiology of pneumococcal infections, which is fundamental to developing novel therapeutic strategies for such infections in immune-compromised patients.

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Role of the TGF‐β pathway in dedifferentiation of human mature adipocytes

et al. 2017

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Dedifferentiation of adipocytes contributes to the generation of a proliferative cell population that could be useful in cellular therapy or tissue engineering. Adipocytes can dedifferentiate into precursor cells to acquire a fibroblast‐like phenotype using ceiling culture, in which the buoyancy of fat cells is exploited to allow them to adhere to the inner surface of a container. Ceiling culture is usually performed in flasks, which limits the ability to test various culture conditions. Using a new six‐well plate ceiling culture approach, we examined the relevance of TGF‐β signaling during dedifferentiation. Adipose tissue samples from patients undergoing bariatric surgery were digested with collagenase, and cell suspensions were used for ceiling cultures. Using the six‐well plate approach, cells were treated with SB431542 (an inhibitor of TGF‐β receptor ALK5) or human TGF‐β1 during dedifferentiation. Gene expression was measured in these cultures and in whole adipose tissue, the stromal–vascular fraction (SVF), mature adipocytes, and dedifferentiated fat (DFAT) cells. TGF‐β1 and collagen type I alpha 1 (COL1A1) gene expression was significantly higher in DFAT cells compared to whole adipose tissue samples and SVF cells. TGF‐β1, COL1A1, and COL6A3 gene expression was significantly higher at day 12 of dedifferentiation compared to day 0. In the six‐well plate model, treatment with TGF‐β1 or SB431542, respectively, stimulated and inhibited the TGF‐β pathway as shown by increased TGF‐β1, TGF‐β2, COL1A1, and COL6A3 gene expression and decreased expression of TGF‐β1, COL1A1, COL1A2, and COL6A3, respectively. Treatment of DFAT cells with TGF‐β1 increased the phosphorylation level of SMAD 2 and SMAD 3. Thus, a new six‐well plate model for ceiling culture allowed us to demonstrate a role for TGF‐β in modulating collagen gene expression during dedifferentiation of mature adipocytes.

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Revisiting the regulatory roles of the TGF-β family of cytokines

Cited by 91 publications

References 61 publications

Reevaluation of Pluripotent Cytokine TGF-β3 in Immunity

Reevaluation of Pluripotent Cytokine TGF-β3 in Immunity

Role of the transforming growth factor (TGF)-β1 and TGF-β1 signaling pathway on the pathophysiology of respiratory pneumococcal infections

Role of the TGF‐β pathway in dedifferentiation of human mature adipocytes

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