 Your new post is loading...
Your new post is loading...
|
Suggested by
Société Francaise d'Immunologie
December 21, 2017 3:24 AM
|
Human CD3+CD4+ Th cells, FOXP3+ T regulatory (Treg) cells, and T regulatory type 1 (Tr1) cells are essential for ensuring peripheral immune response and tolerance, but the diversity of Th, Treg, and Tr1 cell subsets has not been fully characterized. Independent functional characterization of human Th1, Th2, Th17, T follicular helper (Tfh), Treg, and Tr1 cells has helped to define unique surface molecules, transcription factors, and signaling profiles for each subset. However, the adequacy of these markers to recapitulate the whole CD3+CD4+ T cell compartment remains questionable. In this study, we examined CD3+CD4+ T cell populations by single-cell mass cytometry. We characterize the CD3+CD4+ Th, Treg, and Tr1 cell populations simultaneously across 23 memory T cell–associated surface and intracellular molecules. High-dimensional analysis identified several new subsets, in addition to the already defined CD3+CD4+ Th, Treg, and Tr1 cell populations, for a total of 11 Th cell, 4 Treg, and 1 Tr1 cell subsets. Some of these subsets share markers previously thought to be selective for Treg, Th1, Th2, Th17, and Tfh cells, including CD194 (CCR4)+FOXP3+ Treg and CD183 (CXCR3)+T-bet+ Th17 cell subsets. Unsupervised clustering displayed a phenotypic organization of CD3+CD4+ T cells that confirmed their diversity but showed interrelation between the different subsets, including similarity between Th1–Th2–Tfh cell populations and Th17 cells, as well as similarity of Th2 cells with Treg cells. In conclusion, the use of single-cell mass cytometry provides a systems-level characterization of CD3+CD4+ T cells in healthy human blood, which represents an important baseline reference to investigate abnormalities of different subsets in immune-mediated pathologies.
|
|
Suggested by
Société Francaise d'Immunologie
November 21, 2017 1:16 PM
|
Producing suppressive cytokines is a key molecular mechanism for Tregs to conduct
long-range suppressive functions. Wei et al. demonstrated that effector Tregs can
be diversified into two functionally distinct subsets based on IL-35 and IL-10 expression
that work in a complementary way to maintain immune tolerance.
|
Suggested by
LIGHTING
August 25, 2017 9:06 AM
|
The CD4+ lineage–specific transcription factor Thpok is required for intrathymic CD4+ T cell differentiation and, together with its homolog LRF, supports CD4+ T cell helper effector responses. However, it is not known whether these factors are needed for the regulatory T cell (Treg) arm of MHC class II responses. In this study, by inactivating in mice the genes encoding both factors in differentiated Tregs, we show that Thpok and LRF are redundantly required to maintain the size and functions of the postthymic Treg pool. They support IL-2–mediated gene expression and the functions of the Treg-specific factor Foxp3. Accordingly, Treg-specific disruption of Thpok and Lrf causes a lethal inflammatory syndrome similar to that resulting from Treg deficiency. Unlike in conventional T cells, Thpok and LRF functions in Tregs are not mediated by their repression of the transcription factor Runx3. Additionally, we found that Thpok is needed for the differentiation of thymic Treg precursors, an observation in line with the fact that Foxp3+ Tregs are CD4+ cells. Thus, a common Thpok-LRF node supports both helper and regulatory arms of MHC class II responses.
This article is featured in In This Issue , p.[1529][1]
[1]: /lookup/volpage/199/1529
|
Scooped by
Gilbert C FAURE
July 30, 2017 3:08 AM
|
Available evidence indicates that the CD6 lymphocyte surface receptor is involved in T-cell developmental and activation processes, by facilitating cell-to-cell adhesive contacts with antigen presenting cells and likely modulating T-cell receptor (TCR) signaling. Here, we show that in vitro activation of human T-cells under different TCR-ligation conditions leads to surface down-regulation of CD6 expression. This phenomenon was i) concomitant to increased levels of soluble CD6 in culture supernatants, ii) partially reverted by protease inhibitors, iii) no associated down-regulated in CD6 mRNA levels, and iv) reversible by stimulus removal. CD6 down-modulation inversely correlated with up-regulation of CD25 in both FoxP3- (Tact) and FoxP3+ (Treg) cell subsets. Furthermore, ex vivo analysis of peripheral CD4+ and CD8+ T-cells with activated (CD25+) or effector memory (TEM, CD45RA-CCR7-) phenotype present lower CD6 levels than their naïve or central memory (TCM, CD45RA-CCR7+) counterparts. CD6lo/- T-cells resulting from in vitro T-cell activation show higher apoptosis and lower proliferation levels than CD6hi T-cells, supporting the relevance of CD6 in the induction of proper T-cell proliferative responses and resistance to apoptosis. Accordingly, CD6 transfectants also showed higher viability when exposed to TCR-independent apoptosis-inducing conditions in comparison with untransfected cells. Taken together, these results provide insight into the origin of soluble CD6 and the previously reported circulating CD6-negative T-cell subset in humans, as well as into the functional consequences of CD6 down-modulation on ongoing T-cell responses, which includes sensitization to apoptotic events and attenuation of T-cell proliferative responses.
|
|
Scooped by
Gilbert C FAURE
June 30, 2017 1:18 AM
|
CD4 T cells, including T regulatory cells (Treg cells) and effector T helper cells (Th cells), and recently identified innate lymphoid cells (ILCs) play important roles in host defense and inflammation. Both CD4 T cells and ILCs can be classified into distinct lineages based on their functions and the expression of lineage-specific genes, including those encoding effector cytokines, cell surface markers, and key transcription factors. It was first recognized that each lineage expresses a specific master transcription factor and the expression of these factors is mutually exclusive because of cross-regulation among these factors. However, recent studies indicate that the master regulators are often coexpressed. Furthermore, the expression of master regulators can be dynamic and quantitative. In this review, we will first discuss similarities and differences between the development and functions of CD4 T cell and ILC subsets and then summarize recent literature on quantitative, dynamic, and cell type–specific balance between the master transcription factors in determining heterogeneity and plasticity of these subsets.
|
|
Scooped by
Gilbert C FAURE
March 22, 2017 3:57 PM
|
Selective suppression of effector CD4+ T cell functions is necessary to prevent immune cell–mediated damage to healthy tissues. This appears especially true during pregnancy or in individuals predisposed to autoimmunity. Foxp3+ regulatory T (Treg) cells and induction of anergy, an acquired state of T cell functional unresponsiveness in Foxp3− cells, have both been implicated as mechanisms to suppress dangerous immune responses to tissue-restricted self-Ags. Anergic CD4+ T cells and Treg cells share a number of phenotypic and mechanistic traits—including the expression of CD73 and folate receptor 4, and the epigenetic modification of Treg cell signature genes—and an interesting relationship between these two subsets has recently emerged. In this review, we will compare and contrast these two subsets, as well as explore the role of anergy in the generation of peripheral Treg cells.
|
|
Scooped by
Gilbert C FAURE
December 13, 2016 2:18 AM
|
Numerous innate and adaptive immune cells reside in non-lymphoid tissues, where they
contribute to barrier immunity, tissue homeostasis, and immune regulation. These tissue-resident
populations do not recirculate in the blood or lymphatics and adopt a unique phenotype
that is distinct from immune cells in the circulation. Tissue residency has been predominantly
described for memory CD8+ T cells [tissue-resident memory T cells (TRM)], but it is
now clear that CD4 T cells, regulatory T (Treg) cells, various innate T cells, and
innate lymphoid cells (ILCs) can establish residence in non-lymphoid tissues.
|
|
Suggested by
Société Francaise d'Immunologie
August 22, 2016 3:00 AM
|
T regulatory (Treg) cells play important roles in the resolution of inflammation.
Pan and colleagues show that, in turn, inflammatory cues induce the expression of
miR-17, which targets transcriptional co-regulators that act in concert with Foxp3
to diminish the suppressive activity of Treg cells.
|
|
Scooped by
Gilbert C FAURE
February 17, 2016 9:05 AM
|
Regulatory T cells (Treg) are essential for T cell homeostasis and maintenance of peripheral tolerance. They prevent activation of auto-reactive T effector cells (Teff) in the context of autoimmunity and allergy.
|
|
Scooped by
Gilbert C FAURE
February 3, 2016 12:28 PM
|
RT @Cancer_Cell: Munn @MCG_AUG & Mellor @StudentsNCL review IDO in the tumor microenvironment https://t.co/X4LZZSgicQ in Trends Immunol.
|
|
Suggested by
Société Francaise d'Immunologie
November 28, 2015 2:16 PM
|
Immunology: In the right place at the right time Nature.com This cytokine then fuels further Treg-cell proliferation and/or function, and the fully activated Treg cells eventually suppress effector T-cell activation, possibly by acting directly on...
|
|
Scooped by
Gilbert C FAURE
October 6, 2015 4:00 PM
|
Oncotarget. 2015 Sep 29. [Epub ahead of print]
|
|
Scooped by
Gilbert C FAURE
September 28, 2015 9:53 AM
|
|
|
|
Scooped by
Gilbert C FAURE
December 18, 2017 11:16 AM
|
bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution
|
|
Suggested by
Société Francaise d'Immunologie
November 13, 2017 11:34 AM
|
Neuropilins (NRPs) are non-tyrosine kinase cell surface glycoproteins expressed in all vertebrates and widely conserved across species. The two isoforms, NRP1 and NRP2 mainly act as co-receptors for class III Semaphorins and for members of the Vascular Endothelial Growth Factor (VEGF) family of molecules and are widely known for their role in a wide array of physiological processes like cardiovascular, neuronal development and patterning, angiogenesis, lymphangiogenesis as well as various clinical disorders. Intriguingly, additional roles for NRPs occur with myeloid and lymphoid cells, in normal physiological as well as different pathological conditions, including cancer, immunological disorders, and bone diseases. However, little is known concerning the molecular pathways that govern these functions. Additionally, NRP1 expression has been characterized in different immune cellular phenotypes including macrophages, dendritic cells (DCs), and T cell subsets, especially regulatory T cell (Treg) populations. In contrast, the functions of NRP2 in immune cells is less well known. In this Review, we briefly summarize the genomic organization, structure, and binding partners of the NRPs, and extensively discuss the recent advances in their role and function in different immune cell subsets and their clinical implications.
|
|
Scooped by
Gilbert C FAURE
August 7, 2017 6:47 AM
|
Metabolism has been shown to integrate with epigenetics and transcription to modulate cell fate and function. Beyond meeting the bioenergetic and biosynthetic demands of T-cell differentiation, whether metabolism might control T-cell fate by an epigenetic mechanism is unclear. Here, through the discovery and mechanistic characterization of a small molecule, (aminooxy)acetic acid, that reprograms the differentiation of T helper 17 (TH17) cells towards induced regulatory T (iTreg) cells, we show that increased transamination, mainly catalysed by GOT1, leads to increased levels of 2-hydroxyglutarate in differentiating TH17 cells. The accumulation of 2-hydroxyglutarate resulted in hypermethylation of the Foxp3 gene locus and inhibited Foxp3 transcription, which is essential for fate determination towards TH17 cells. Inhibition of the conversion of glutamate to α-ketoglutaric acid prevented the production of 2-hydroxyglutarate, reduced methylation of the Foxp3 gene locus, and increased Foxp3 expression. This consequently blocked the differentiation of TH17 cells by antagonizing the function of transcription factor RORγt and promoted polarization into iTreg cells. Selective inhibition of GOT1 with (aminooxy)acetic acid ameliorated experimental autoimmune encephalomyelitis in a therapeutic mouse model by regulating the balance between TH17 and iTreg cells. Targeting a glutamate-dependent metabolic pathway thus represents a new strategy for developing therapeutic agents against TH17-mediated autoimmune diseases.
|
|
Suggested by
LIGHTING
July 3, 2017 2:07 AM
|
Regulatory T cells (Tregs) restrict over-exuberant lymphocyte activation. While close proximity between Tregs and their suppression targets is important for optimal inhibition, and literature indicates that draining lymph nodes may serve as a prime location for the suppression, signaling details orchestrating this event are not fully characterized. Using a protocol to enable peripheral generation of inducible antigen-specific Tregs (asTregs) to control allergen-induced asthma, we have identified an antigen-specific mechanism that locks asTregs within hilar LNs which in turn suppresses airway inflammation. The suppressive asTregs, upon antigen stimulation in the lymph node, downregulate S1p1 (Sphingosine-1-phosphate receptor 1) egress receptor expression. These asTregs in turn mediate the downregulation of the same receptor on incoming effector T cells. Therefore, asTregs and effector T cells are locked in these draining lymph nodes for prolonged interactions. Disruption of individual steps of this retention sequence abolishes the inflammation controlled by asTregs. Collectively, this study identifies a new requirement of spatial congregation with their suppression targets essential for asTreg functions, and suggests therapeutic programs via Treg traffic control.
|
|
Suggested by
LIGHTING
May 18, 2017 11:20 AM
|
Hippo signaling controls cell and tissue growth. Geng et al. show that Hippo signaling is required for TH17 cell differentiation but inhibits Treg cell differentiation.
|
|
Suggested by
LIGHTING
December 18, 2016 11:04 AM
|
Highlights •Transcriptome analysis performed on tumor-resident CD4+ Th1, Th17, and Treg cells •Tumor-infiltrating Treg cells are defined by the expression of signature genes •Treg-specific signature genes correlate with patients’ survival in both CRC and NSCLC Summary
Via Krishan Maggon
Regulatory T cells (TReg cells), a specialized T cell lineage, have a pivotal function in the control of self tolerance and inflammatory responses. Recent studies have revealed a discrete mode of T cell receptor (TCR) signalling that regulates TReg cell differentiation, maintenance and function and that affects gene expression, metabolism, cell adhesion and migration of these cells. Here, we discuss the emerging understanding of TCR-guided differentiation of TReg cells in the context of their function in health and disease.
Via Krishan Maggon
|
|
Scooped by
Gilbert C FAURE
February 16, 2016 3:49 AM
|
Treg derived IL-35 limits anti-tumor T cell immunity
|
|
Scooped by
Gilbert C FAURE
January 16, 2016 3:40 AM
|
Early life differentiation and regulatory function of human T cells is confined to particular anatomical sites.
|
|
Suggested by
Société Francaise d'Immunologie
November 5, 2015 2:53 PM
|
|
|
Suggested by
Société Francaise d'Immunologie
October 6, 2015 3:17 PM
|
Regulatory T (Treg) cells have a critical role in the control of immunity, and their diverse subpopulations may allow adaptation to different types of immune responses.
|
