Lineage specification and heterogeneity of T follicular helper cells

Yu, Di; Batten, Marcel; Mackay, Charles R.; King, Charles M.

doi:10.1016/j.coi.2009.09.013

Cited by 53 publications

(52 citation statements)

References 68 publications

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“…10 These interactions drive B-cell differentiation towards extrafollicular short-lived plasma blasts and intrafollicular long-lived plasma cells, which produce antibodies, as well as the formation of memory B cells. [10][11][12][13] The transcriptional repressor B-cell lymphoma 6 seems to regulate the genetic program of CD4Tfh cell differentiation and is a suitable biomarker that is useful in distinguishing these cells from other CD4 T cells (e.g. Th1, Th2, Th17, and T-regulatory).…”

Section: Introductionmentioning

confidence: 99%

T follicular helper expansion and humoral-mediated rejection are independent of the HVEM/BTLA pathway

et al. 2016

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Section: Introductionmentioning

confidence: 99%

T follicular helper expansion and humoral-mediated rejection are independent of the HVEM/BTLA pathway

et al. 2016

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“…Several reports suggest that miRNAs prevent naïve T cells from committing prematurely to helper functions [35][36][37]. Upon TCR activation, most miRNAs were shown to be downregulated as a result of the degradation of the Argonaute miRNA-processing proteins, and naïve T cells with lower Argonaute2 levels were more prone to differentiate into cytokine-producing T cells [19].…”

Section: Mirna-mediated Regulation Of Cytokine Production By T Cellsmentioning

confidence: 99%

Cross‐regulation between cytokine and microRNA pathways in T cells

et al. 2015

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microRNA (miRNA) mediated regulation of protein expression has emerged as an important mechanism in T-cell physiology, from development and survival to activation, proliferation, and differentiation. One of the major classes of proteins involved in these processes are cytokines, which are both key input signals and major products of T-cell function. Here, we summarize the current data on the molecular cross-talk between cytokines and miRNAs: how cytokines regulate miRNA expression, and how specific miRNAs control cytokine production in T cells. We also describe the inflammatory consequences of deregulating the miRNA/cytokine axis in mice and humans. We believe this topical area will have key implications for immune modulation and treatment of autoimmune pathology. Keywords:Cytokines r Inflammation r miRNA r T cells microRNAs as regulators of protein expressionBiological processes require the integration of environmental stimuli at the level of gene expression. The robustness of genetic networks depends on the distinction between physiological responses (to particular cues) and biological "noise" (stochastic variations), which can be achieved, for example, by establishing feed-forward transcriptional loops. Over the past two decades, a new mechanism that interacts with transcriptional loops and sets additional thresholds, which enable cells to filter physiological signals from noise has emerged; this mechanism regulates gene expression at the posttranscriptional level and relies on microRNAs (miRNAs; reviewed in [1]). These are an abundant class of evolutionarily conserved small noncoding (untranslated) RNA species that control target mRNA stability, degradation, and translation, thus affecting the majority of mammalian genes [2].Correspondence: Dr. Anita Q. Gomes e-mail: anitagomes@medicina.ulisboa.ptIn the conventional miRNA biogenesis pathway, RNA polymerase II transcribed pri-miRNAs are processed by the nuclear RNase III enzyme Drosha (complexed with DGCR8) to generate 60-70 nt stem-loop intermediates, the pre-miRNAs, that are further processed into 19-24mers in the cytoplasm by another key RNase III, Dicer. Mature miRNAs are then incorporated into RNAinduced silencing complexes, whose core components are proteins of the Argonaute family (Ago1-4), which use the 5 end (nucleotides 2-8) "seed sequence" of the miRNA to recognize complementary mRNA transcripts (mostly in their 3 untranslated region) for deadenylation or inhibition of translation, ultimately resulting in mRNA decapping and decay (reviewed in [3,4]).Unique spatial and temporal expression patterns in distinct hematopoietic cell lineages are suggestive of multiple roles for miRNAs in hematopoiesis, self-tolerance, and in immune responses, which have been explored over the past decade (reviewed in [5,6]). Over a 100 different miRNAs have been shown to be expressed by cells of the immune system, where * These authors contributed equally to this work as first authors. * * These authors contributed equally to this work as last authors.C 2015 WILEY-VCH Ve...

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“…10 Recent reports described that TFH cells can produce significant amounts of IL-4, interferon-γ and IL-17 which are normally associated with TH2, TH1 and TH17 cells, respectively. 1,11 Thus, TFH cells share phenotypic features with other TH cell lineages raising the question of whether TFH cells really do constitute a distinct lineage or whether they result from a conversion of effector TH cells that acquire TFH cell functions.…”

Section: Lineage and Differentiation Of Follicular T-helper Cellsmentioning

confidence: 99%

“…Indeed, naïve T cells that express CD62L and CCR7 enter secondary lymphoid organs in the T-cell zones. 8,11 Up-regulation of CXCR5, the receptor for CXCL13, a chemokine produced by follicular dendritic cells which promotes B-cell entry into the follicle, occurs after the interaction between antigen-presenting cells and naïve TH cells.…”

Section: 11mentioning

confidence: 99%

A novel subset of T-helper cells: follicular T-helper cells and their markers

Laurent¹,

Fazilleau²,

Brousset³

2010

Haematologica

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ML, et al. Mutations in the genes coding for the NF-{kappa}B regulating factors IκBα and A20 are uncommon in nodular lymphocyte-predominant Hodgkin lymphoma. Haematologica. 2010; 95(1) 1 TFH cells are characterized by their homing capacity in CXCL13-rich areas, such as B-cell follicles, through CXCR5 expression and their ability to support immunoglobulin production. The differentiation and homing of TFH, as well as their interactions with B cells, have been the subject of intense research and several markers have been identified as components of the TFH signature. Thanks to gene expression profiling carried out on peripheral T-cell lymphomas, a TFH signature has been reported in angioimmunoblastic T-cell lymphoma (AITL) and in follicular T-cell lymphoma.2-4 Several markers that identify TFH cells are now used in hematopathology to reinforce the diagnostic criteria of AITL. In this issue of the Journal, Marafioti et al.5 describe that inducible T-cell co-stimulatory molecule (ICOS), a CD28 homolog implicated in the regulation of T-cell differentiation and function, appears to be a relevant marker for the diagnosis of TFH-derived lymphoma such as AITL and follicular T-cell lymphoma. This review first summarizes the recent evidence on TFH cell differentiation and the present state of knowledge on molecules expressed by TFH cells. Then, from this perspective, the potential implications of TFH cells in lymphomagenesis and as part of the tumor microenvironment are covered. Lineage and differentiation of follicular T-helper cellsTH cell responses are heterogeneous and effector function choice is imposed during initial activation of the naïve TH cells through the expression of transcription factors. It is now clear that TFH cells belong to a subset of TH cells that differ from the other TH cell subsets. Indeed, TH1 cells express STAT4, STAT1 and T-box transcription factor/Tbet, TH2 cells express GATA3, TH17 cells express retinoid related orphan receptor (RORγt) and regulatory T cells (Treg) express FOXP3. It has recently been shown that the TFH cell differentiation program is controlled by BCL6. 6,7 TFH cells upregulate BCL6 which in turn blocks TH1, TH2 and TH17 cell differentiation by repressing their selective transcription factors. 6 Moreover, BCL6 antagonizes the expression of Blimp-1 transcription factor, which is preferentially expressed by TH cells in the T zone area. 6,8 BCL6 also represses the expression of miR-17-92, a micro RNA that down-regulates CXCR5 expression, which is essential for TFH cell function. Finally over-expression of BCL6 in activated TH cells induces expression of interleukin (IL)-6 receptor and IL-21 receptor, which are both required for TFH cell generation as shown by the role of IL-6 and IL-21 in TFH cell differentiation.9 ICOS is also implicated in the regulation of TFH cell differentiation. Once engaged with its ligand (ICOS-L), expressed on antigen-presenting cells including B cells, ICOS induces the production of helper cytokines such as IL-2, IL-4 and especially IL-10 and IL-21.10 I...

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Lineage specification and heterogeneity of T follicular helper cells

Cited by 53 publications

References 68 publications

T follicular helper expansion and humoral-mediated rejection are independent of the HVEM/BTLA pathway

T follicular helper expansion and humoral-mediated rejection are independent of the HVEM/BTLA pathway

Cross‐regulation between cytokine and microRNA pathways in T cells

A novel subset of T-helper cells: follicular T-helper cells and their markers

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