The role of transforming growth factor <i>β</i> in T helper 17 differentiation

Zhang, Song

doi:10.1111/imm.12938

Cited by 122 publications

(86 citation statements)

References 171 publications

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“…In our experiments, TGFβ, which is reported to be important in inducing Th17 differentiation (reviewed by Zhang et al 38 ), was produced by T cells cultured with IFNγ-pretreated KCs ( Figure S5B). In combination with IL-6, small amounts of TGFβ are sufficient to trigger Th17 differentiation.…”

Section: Discussionsupporting

confidence: 50%

“…Since the specific cytokine milieu ultimately dictates T cell differentiation, this finding indicated that the CD58/CD2 interaction may be important in Th1 differentiation. In contrast, transforming growth factor β (TGFβ), a cytokine crucially involved in Th17 differentiation, 38 was equally produced in naive T cells cultured with IFNγ-pretreated KCs, regardless of whether CD58/CD2 signaling was blocked ( Fig. 5b).…”

Section: Keratinocyte-initiated Th1 Differentiation Is Dependent On Cmentioning

confidence: 99%

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Keratinocytes costimulate naive human T cells via CD2: a potential target to prevent the development of proinflammatory Th1 cells in the skin

et al. 2019

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The interplay between keratinocytes and immune cells, especially T cells, plays an important role in the pathogenesis of chronic inflammatory skin diseases. During psoriasis, keratinocytes attract T cells by releasing chemokines, while skin-infiltrating selfreactive T cells secrete proinflammatory cytokines, e.g., IFNγ and IL-17A, that cause epidermal hyperplasia. Similarly, in chronic graftversus-host disease, allogenic IFNγ-producing Th1/Tc1 and IL-17-producing Th17/Tc17 cells are recruited by keratinocyte-derived chemokines and accumulate in the skin. However, whether keratinocytes act as nonprofessional antigen-presenting cells to directly activate naive human T cells in the epidermis remains unknown. Here, we demonstrate that under proinflammatory conditions, primary human keratinocytes indeed activate naive human T cells. This activation required cell contact and costimulatory signaling via CD58/CD2 and CD54/LFA-1. Naive T cells costimulated by keratinocytes selectively differentiated into Th1 and Th17 cells. In particular, keratinocyte-initiated Th1 differentiation was dependent on costimulation through CD58/CD2. The latter molecule initiated STAT1 signaling and IFNγ production in T cells. Costimulation of T cells by keratinocytes resulting in Th1 and Th17 differentiation represents a new explanation for the local enrichment of Th1 and Th17 cells in the skin of patients with a chronic inflammatory skin disease. Consequently, local interference with T cell-keratinocyte interactions may represent a novel strategy for the treatment of Th1 and Th17 cell-driven skin diseases.In addition, in chronic graft-versus-host disease (GVHD), a major complication of allogenic stem cell transplantation, the KCmediated secretion of chemokines (CXCL9 and CXCL10) leads to the recruitment of alloreactive T cells into the skin. 14 These allogenic T cells predominantly belong to the IFNγ-producing Th1/ Tc1 and IL-17-producing Th17/Tc17 subpopulations and cause cutaneous manifestations, e.g., follicular erythema. [15][16][17] Although the pivotal role of KCs in non-contact-mediated communication during chronic skin inflammation is quite well understood, the direct interaction between KCs and T cells remains elusive. In particular, the potential of KCs to act as nonprofessional APCs, enabling them to costimulate T cells directly in the skin, is still debated.T cells require two distinct signals for activation and clonal expansion. The first signal is transmitted by the antigen-specific T cell receptor (TCR) on T cells, following recognition of antigenic peptides loaded on MHC class I or class II molecules expressed by APCs. The first signal secures the antigen specificity of the immune reaction. The second signal is transmitted through costimulatory receptors, dictating the progression to T cell activation. Between

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Section: Discussionsupporting

confidence: 50%

Section: Keratinocyte-initiated Th1 Differentiation Is Dependent On Cmentioning

confidence: 99%

Keratinocytes costimulate naive human T cells via CD2: a potential target to prevent the development of proinflammatory Th1 cells in the skin

et al. 2019

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“…In contrast, mogroside V significantly increased the production of TGF‐β in our asthmatic mice. TGF‐β, as an anti‐inflammatory cytokine generated by Tregs, has been reported to effectively modulate the differentiation and activation of Th17 cells and to reduce airway inflammation in a study on asthmatic animals (Zhang, ; Zhao & Wang, ). We also found that mogroside V effectively reduces the pulmonary levels of IL‐17A and IL‐23 mRNA expression in the asthmatic mice.…”

Section: Discussionmentioning

confidence: 99%

“…Forkhead/winged helix transcription factor p3 (Foxp3) is a specific transcription factor that is necessary and sufficient for promoting the development of Tregs and maintaining their normal function (Chen et al, ). Activation of Foxp3 can regulate the production of some anti‐inflammatory cytokines, such as IL‐10 and transforming growth factor (TGF) β and reduces the upregulation of Th2 cytokines; these effects modulate autoimmunity and immune tolerance (Zhang, ). Retinoid acid receptor‐related orphan receptor (RORγt) has been reported as a necessary factor for differentiation of precursors into Th17 cells and maintains the secretion of IL‐17A (Lazarevic et al, ; Park et al, ).…”

Section: Introductionmentioning

confidence: 99%

Protective activity of mogroside V against ovalbumin‐induced experimental allergic asthma in Kunming mice

et al. 2019

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We investigated the antiasthmatic effect of mogroside V (Mog V) in mice with ovalbumin (OVA)‐induced asthma. Administration of Mog V effectively attenuated OVA‐induced airway hyperresponsiveness and reduced the number of inflammatory cells in bronchoalveolar lavage fluid (BALF). Histological examination showed that Mog V reduced the inflammatory infiltration of the lungs in the asthmatic mice. ELISAs suggested that Mog V effectively decreased the levels of IL‐4, IL‐5, and IL‐13 in BALF and serum levels of OVA‐specific IgE and IgG1 in the asthmatic mice. A quantitative reverse‐transcription PCR assay also indicated that Mog V decreased the mRNA levels of IL‐17A, IL‐23, and RORγt in the lungs of the asthmatic mice (the opposite effect on Foxp3 mRNA). Furthermore, Mog V significantly reduced the OVA‐induced activation of NF‐κB in the lungs. This study indicates that Mog V alleviates OVA‐induced inflammation in airways, and this effect is associated with a reduction in NF‐κB activation. Practical applications A traditional Chinese medicine herb has been reported to have a strong curative effect on asthma in clinical practice. Siraitia grosvenorii is known in China as a functional food product with the ability to improve lung function. Mogroside V is a triterpene glycoside isolated from S. grosvenorii. Nonetheless, the antiasthmatic effect of mogroside V has not been evaluated yet. The aim of this study was to investigate the antiasthmatic activity of mogroside V in mice with chemically induced asthma. The data from this study will provide some scientific evidence supporting wider use of S. grosvenorii in functional foods.

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“…The Th17 phenotype is induced by a combination of IL6, IL23 and TGFβ1 [31][32][33], and functionally by the amplitude of TGFβ1 [71]. Th17 cells have a dual-state plasticity; a high TGFβ1 induces regulatory or immunetolerizing effects while low TGFβ1 allows a Th1-like cytotoxic response that includes IFNγ and TNFα [34,36,37].…”

Section: T-helper Cytotoxic Pathways (Th1 Th17 Pathways)mentioning

confidence: 99%

Cytokine network analysis of immune responses before and after autologous dendritic cell and tumor cell vaccine immunotherapies in a randomized trial

Nistor¹,

Dillman²

2020

J Transl Med

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Background: In a randomized phase II trial conducted in patients with metastatic melanoma, patient-specific autologous dendritic cell vaccines (DCV) were associated with longer survival than autologous tumor cell vaccines (TCV). Both vaccines presented antigens from cell-renewing autologous tumor cells. The current analysis was performed to better understand the immune responses induced by these vaccines, and their association with survival. Methods: 110 proteomic markers were measured at a week-0 baseline, 1 week before the first of 3 weekly vaccine injections, and at week-4, 1 week after the third injection. Data was presented as a deviation from normal controls. A two-component principal component (PC) statistical analysis and discriminant analysis were performed on this data set for all patients and for each treatment cohort. Results: At baseline PC-1 contained 64.4% of the variance and included the majority of cytokines associated with Th1 and Th2 responses, which positively correlated with beta-2-microglobulin (B2M), programmed death protein-1 (PD-1) and transforming growth factor beta (TGFβ1). Results were similar at baseline for both treatment cohorts. After three injections, DCV-treated patients showed correlative grouping among Th1/Th17 cytokines on PC-1, with an inverse correlation with B2M, FAS, and IL-18, and correlations among immunoglobulins in PC-2. TCV-treated patients showed a positive correlation on PC-1 among most of the cytokines and tumor markers B2M and FAS receptor. There were also correlative changes of IL12p40 with both Th1 and Th2 cytokines and TGFβ1. Discriminant analysis provided additional evidence that DCV was associated with innate, Th1/Th17, and Th2 responses while TCV was only associated with innate and Th2 responses. Conclusions: These analyses confirm that DCV induced a different immune response than that induced by TCV, and these immune responses were associated with improved survival. Trial registration Clinical trials.gov NCT004936930 retrospectively registered

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The role of transforming growth factor β in T helper 17 differentiation

Cited by 122 publications

References 171 publications

Keratinocytes costimulate naive human T cells via CD2: a potential target to prevent the development of proinflammatory Th1 cells in the skin

Keratinocytes costimulate naive human T cells via CD2: a potential target to prevent the development of proinflammatory Th1 cells in the skin

Protective activity of mogroside V against ovalbumin‐induced experimental allergic asthma in Kunming mice

Cytokine network analysis of immune responses before and after autologous dendritic cell and tumor cell vaccine immunotherapies in a randomized trial

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