Posttranscriptional T cell gene regulation to limit Tfh cells and autoimmunity

Jiang, Simon; Shen, Nan; Vinuesa, Carola G.

doi:10.1016/j.coi.2015.09.003

Cited by 14 publications

(11 citation statements)

References 87 publications

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“…As a recently identified CD4 + T cell subset, Tfh cells, have been found to be present in GCs, provide selection signals and developmental cues for the proliferation, differentiation and class switching of antigen-selected high-affinity GC B cells [19][20][21][22] . The phenotypic and functional features of Tfh cells include expression of the chemokine receptor CXCR5, costimulatory molecules such as inducible T cell costimulatory (ICOS), programmed Scientific RepoRts | 6:38115 | DOI: 10.1038/srep38115 death 1 (PD-1), as well as the master transcription factor B-cell CLL/lymphoma-6 (Bcl-6) and the cytokine interleukin-21 (IL-21) 19 .…”

mentioning

confidence: 99%

Artemisinin analogue SM934 attenuate collagen-induced arthritis by suppressing T follicular helper cells and T helper 17 cells

Lin

Yang

Zhu

et al. 2016

Sci Rep

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SM934 is an artemisinin analogue with immunosuppressive properties and potent therapeutic activity against lupus-like diseases in autoimmune mice. In this report, the therapeutic efficacy and underlying mechanisms of SM934 on rheumatoid arthritis (RA) was investigated using collagen-induced arthritis (CIA) in DBA/1J mice. We demonstrated that SM934 treatment alleviate the severity of arthritis in CIA mice with established manifestations. The therapeutic benefits were associated with ameliorated joint swelling and reduced extent of bone erosion and destruction. Further, administration of SM934 diminished the development of T follicular helper (Tfh) cells and Th17 cells and suppressed the production of pathogenic antibodies, without altering the proportion of germinal center B cells. Ex vivo, SM934 treatment inhibited the bovine type II collagen (CII) induced proliferation and inflammatory cytokines secretion of CII -reactive T cells. In vitro, SM934 impeded the polarization of naïve CD4+ T cells into Tfh cells and the expression of its transcript factor Bcl-6. Moreover, SM934 decreased the IL-21-producing CD4+ T cells and dampened the IL-21 downstream signaling through STAT3. These finding offered the convincing evidence that artemisinin derivative might attenuate RA by simultaneously interfering with the generation of Tfh cells and Th17 cells as well as the subsequent antibody-mediated immune responses.

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mentioning

confidence: 99%

Artemisinin analogue SM934 attenuate collagen-induced arthritis by suppressing T follicular helper cells and T helper 17 cells

Lin

Yang

Zhu

et al. 2016

Sci Rep

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“…82 Micro-RNAs target mRNAs for degradation and/or suppress their translation. 83 MiR-146a is highly expressed in Tfh cells and in its absence there is an accumulation of Tfh cells. 84 MiR-146a represses multiple canonical Tfh cell transcripts including Icos, Slamf1, Cd84, Stat1, Cxcr4 and Notch1.…”

Section: Presentation Of Antigen By B Cellsmentioning

confidence: 99%

“…In addition, ICOS expression is regulated by the micro‐RNA, MiR‐146a . Micro‐RNAs target mRNAs for degradation and/or suppress their translation . MiR‐146a is highly expressed in Tfh cells and in its absence there is an accumulation of Tfh cells .…”

Section: The Importance Of Co‐receptor Signals In Tfh Cell Differentimentioning

confidence: 99%

Signals that drive T follicular helper cell formation

Webb

Linterman

2017

Immunology

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SummaryT follicular helper (Tfh) cells are a distinct type of CD4 + T cell specialized in providing help to B cells during the germinal centre (GC) reaction. As such, they are critical determinants of the quality of an antibody response following antigen challenge. Excessive production of Tfh cells can result in autoimmunity whereas too few can result in inadequate protection from infection. Hence, their differentiation and maintenance must be tightly regulated to ensure appropriate but limited help to B cells. Unlike the majority of other CD4 + T-cell subsets, Tfh cell differentiation occurs in three phases defined by their anatomical location. During each phase of differentiation the emerging Tfh cells express distinct patterns of coreceptors, which work together with the T-cell receptor (TCR) to drive Tfh differentiation. These signals provided by both TCR and co-receptors during Tfh differentiation alter proliferation, survival, metabolism, cytokine production and transcription factor expression. This review will discuss how engagement of TCR and co-receptors work together to shape the formation and function of Tfh cells.

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“…A role for RNA methylation has yet to be established in renal disease, though one immediate area it may manifest in is immune function, where post-transcriptional regulation of T-cell memory (and by extension transcriptional memory) by T-cell miRNAs and methylation may be dysregulated. Precedence for this has already been established in systemic lupus erythematosus (SLE), where it contributes to tissue damage and auto-antibody formation [57].…”

Section: Rna Methylationmentioning

confidence: 99%

Current epigenetic aspects the clinical kidney researcher should embrace

et al. 2017

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Chronic kidney disease (CKD), affecting 10-12% of the world's adult population, is associated with a considerably elevated risk of serious comorbidities, in particular, premature vascular disease and death. Although a wide spectrum of causative factors has been identified and/or suggested, there is still a large gap of knowledge regarding the underlying mechanisms and the complexity of the CKD phenotype. Epigenetic factors, which calibrate the genetic code, are emerging as important players in the CKD-associated pathophysiology. In this article, we review some of the current knowledge on epigenetic modifications and aspects on their role in the perturbed uraemic milieu, as well as the prospect of applying epigenotype-based diagnostics and preventive and therapeutic tools of clinical relevance to CKD patients. The practical realization of such a paradigm will require that researchers apply a holistic approach, including the full spectrum of the epigenetic landscape as well as the variability between and within tissues in the uraemic milieu.

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Posttranscriptional T cell gene regulation to limit Tfh cells and autoimmunity

Cited by 14 publications

References 87 publications

Artemisinin analogue SM934 attenuate collagen-induced arthritis by suppressing T follicular helper cells and T helper 17 cells

Artemisinin analogue SM934 attenuate collagen-induced arthritis by suppressing T follicular helper cells and T helper 17 cells

Signals that drive T follicular helper cell formation

Current epigenetic aspects the clinical kidney researcher should embrace

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