scholarly journals The Critical Role of Bach2 in Shaping the Balance between CD4+ T Cell Subsets in Immune-Mediated Diseases

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Lingyi Yang ◽  
Shuli Chen ◽  
Qiuyu Zhao ◽  
Ying Sun ◽  
Hong Nie
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Cell Biology ◽  
Transcriptional Activity ◽  
Critical Role ◽  
T Cell Subsets ◽  
B Cell Differentiation ◽  
Immune Mediated ◽  
B And T Lymphocytes

The transcription factor Bach2 which is predominantly expressed in B and T lymphocytes represses the expression of genes by forming heterodimers with small Maf and Batf proteins and binding to the corresponding sequence on the DNA. In this way, Bach2 serves as a highly conserved repressor which controls the terminal differentiation and maturation of both B and T lymphocytes. It is required for class switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes in activated B cells, and its function in B cell differentiation has been well-described. Furthermore, emerging data show that Bach2 regulates transcriptional activity in T cells at super enhancers or regions of high transcriptional activity, thus stabilizing immunoregulatory capacity and maintaining T cell homeostasis. Bach2 is also critical for the formation and function of CD4+ T cell lineages (Th1, Th2, Th9, Th17, T follicular helper (Tfh), and regulatory T (Treg) cells). Genetic variations within Bach2 locus are associated with numerous immune-mediated diseases including multiple sclerosis (MS), rheumatoid arthritis (RA), chronic pancreatitis (CP), type 2 chronic airway inflammation, inflammatory bowel disease (IBD), and type 1 diabetes. Here, we reveal a critical role of Bach2 in regulating T cell biology and the correlation with these immune-mediated diseases.

T Lymphocytes: The “Cellular” Arm of Acquired Immunity in the Peritoneum

2006 ◽  
Vol 26 (4) ◽  
pp. 438-448 ◽  
Author(s):  
Amir Glik ◽  
Amos Douvdevani
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Antigen Presentation ◽  
Cell Population ◽  
Cell Biology ◽  
Specific Antigen ◽  
Acquired Immunity ◽  
Polymorphonuclear Cells

T cells are an important part of the acquired immune response and target specific antigen with their T cell receptor. The peritoneum is a special milieu within which T cells react. We describe briefly the anatomy important for T cell function. T cell biology including antigen presentation, T cell activation, and the different T cell subpopulations are reviewed. We also define innate and acquired immunity and describe the role of polymorphonuclear cells and peritoneal mesothelial cells in the regulation of leukocyte population recruitment during peritonitis. We focus particularly on peritoneal lymphocytes and compare them to the regular lymphocyte populations in the circulation. We illustrate the role of PMCs in antigen presentation and discuss the changes of CD4+ helper T cell subtypes (Th1 and Th2) during peritoneal dialysis. The role of CD8+ cytotoxic T lymphocytes and their possible destructive role for the peritoneal membrane modified by advanced glycation end products are discussed. Polymorphonuclear cells play an important role in the regulation of inflammation and immunity. We describe their possible role in supporting T cells and particularly for generating memory CD8+ T cells by secretion of interleukin-15, a potent T cell growth factor. Light is shed on γδ T cells, a special T cell population that is able to recognize antigens without the restriction of antigen presentation. We end our review with a description of regulatory T cells. This cell population is extremely important in preventing autoimmunity and in the regulation of acquired immunity.

scholarly journals TGF-β Signaling in Cancer: Control by Negative Regulators and Crosstalk with Proinflammatory and Fibrogenic Pathways

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 384 ◽  
Author(s):  
Hendrik Ungefroren
Keyword(s):  
T Cell ◽  
Cell Biology ◽  
Transforming Growth Factor ◽  
T Cell Subsets ◽  
Negative Regulators ◽  
Inflammatory Signaling ◽  
Mesenchymal Transition ◽  
Smad Signaling ◽  
Anti Inflammatory

The transforming growth factor-β (TGF-β) family of secreted growth factors controls many aspects of cell and tissue physiology in multicellular eukaryotes. Dysregulation of its pathway contributes to a broad variety of pathologies, including fibrosis and cancer. TGF-β acts as a powerful tumor suppressor in epithelial cells but during later stages of tumor development cancer cells eventually respond to this cytokine with epithelial-mesenchymal transition (EMT), invasion, metastasis, and immunosuppression. This collection of articles covers some important aspects of TGF-β signaling in cancer. Two articles focus on the role of TGF-β in tumor immunity and pro- and anti-inflammatory signaling, with one analyzing its impact on T-cell biology and different T-cell subsets, while the other deals with modulation of anti-inflammatory signaling by TGF-β receptors through proinflammatory signaling by immune receptors and the role of mechanotransduction in TGF-β-dependent immunosuppression. Another set of four chapters highlights the fact that context-dependent responsiveness to TGF-β is largely controlled by inputs from negative regulators and cooperation with proinflammatory and proapoptotic pathways. This theme is extended to the regulation of Smad signaling by differential phosphorylation, eventually converting canonical Smad signaling to a mitogenic, fibrogenic and carcinogenic outcome. Last, it is discussed how another posttranslational modification, SUMOylation, can modify protein function and impact TGF-β-induced EMT, invasion and metastasis.

scholarly journals Th17 Cell-Mediated Colitis Is Positively Regulated by Interferon Regulatory Factor 4 in a T Cell-Extrinsic Manner

2021 ◽  
Vol 11 ◽  
Author(s):  
Vera Buchele ◽  
Patrick Konein ◽  
Tina Vogler ◽  
Timo Kunert ◽  
Karin Enderle ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Th17 Cell ◽  
Interferon Regulatory Factor ◽  
T Cell Subsets ◽  
Regulatory Factor ◽  
Th17 Response ◽  
Immune Mediated ◽  
Interferon Regulatory Factor 4

Inflammatory bowel diseases (IBDs) are characterized by chronic, inflammatory gastrointestinal lesions and often require life-long treatment with immunosuppressants and repetitive surgical interventions. Despite progress in respect to the characterization of molecular mechanisms e.g. exerted by TNF-alpha, currently clinically approved therapeutics fail to provide long-term disease control for most patients. The transcription factor interferon regulatory factor 4 (IRF4) has been shown to play important developmental as well as functional roles within multiple immune cells. In the context of colitis, a T cell-intrinsic role of IRF4 in driving immune-mediated gut pathology is established. Here, we conversely addressed the impact of IRF4 inactivation in non-T cells on T cell driven colitis in vivo. Employing the CD4+CD25− naïve T cell transfer model, we found that T cells fail to elicit colitis in IRF4-deficient compared to IRF4-proficient Rag1−/− mice. Reduced colitis activity in the absence of IRF4 was accompanied by hampered T cell expansion both within the mesenteric lymph node (MLN) and colonic lamina propria (cLP). Furthermore, the influx of various myeloids, presumably inflammation-promoting cells was abrogated overall leading to a less disrupted intestinal barrier. Mechanistically, gene profiling experiments revealed a Th17 response dominated molecular expression signature in colon tissues of IRF4-proficient, colitic Rag1−/− but not in colitis-protected Rag1−/−Irf4−/− mice. Colitis mitigation in Rag1−/−Irf4−/− T cell recipients resulted in reduced frequencies and absolute numbers of IL-17a-producing T cell subsets in MLN and cLP possibly due to a regulation of conventional dendritic cell subset 2 (cDC2) known to impact Th17 differentiation. Together, extending the T cell-intrinsic role for IRF4 in the context of Th17 cell driven colitis, the provided data demonstrate a Th17-inducing and thereby colitis-promoting role of IRF4 through a T cell-extrinsic mechanism highlighting IRF4 as a putative molecular master switch among transcriptional regulators driving immune-mediated intestinal inflammation through both T cell-intrinsic and T cell-extrinsic mechanisms. Future studies need to further dissect IRF4 controlled pathways within distinct IRF4-expressing myeloid cell types, especially cDC2s, to elucidate the precise mechanisms accounting for hampered Th17 formation and, according to our data, the predominant mechanism of colitis protection in Rag1−/−Irf4−/− T cell receiving mice.

scholarly journals An imbalance of esophageal effector and regulatory T cell subsets in experimental eosinophilic esophagitis in mice

2009 ◽  
Vol 297 (3) ◽  
pp. G550-G558 ◽  
Author(s):  
Xiang Zhu ◽  
Meiqin Wang ◽  
Caleb H. Crump ◽  
Anil Mishra
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Eosinophilic Esophagitis ◽  
Critical Role ◽  
T Cell Subsets ◽  
Activation Markers ◽  
Activated T Cell ◽  
Anti Inflammatory Cytokine

We recently reported a critical role for T cells in the induction of eosinophilic esophagitis (EE) in mice; however, the role of specific T cell subsets in disease pathogenesis is not yet understood. In the current study, we tested the hypothesis that allergen-induced EE develops in response to the disproportion of functionally different effector and regulatory T cells in the esophagus. Fluorescence-activated cell sorter analysis was performed to examine activated T cell subsets using the cell surface activation markers CD25 and CD69. A significant increase in activated CD4+ and CD4− T cells was observed in the total esophageal cells isolated from the mouse model of EE. Furthermore, an imbalance in the effector and regulatory T cells was observed in the esophagus. The esophageal CD4+CD45RBhigh effector T cells in allergen-challenged mice increased compared with saline-challenged mice (65.4 ± 3.6 × 103 to 44.8 ± 4.2 × 103), whereas CD4+CD45RBlow mostly regulatory T cells decreased in allergen-challenged mice compared with saline-challenged mice (5.8 ± 0.9 × 103 from 10.2 ± 1.7 × 103). The functional characteristics were examined by analysis of the pro- and anti-inflammatory cytokine profile of purified low and high CD4+CD45RB subsets from the spleen. Additionally, a significantly reduced interleukin (IL)-2 production by CD4+CD45RBlow cells in allergen-challenged mice compared with saline-challenged mice was observed. The reduced IL-2 in the CD4+CD45RBlow subset may be associated with reduction of CD4+CD45RBlow subset. In conclusion, our results suggest that local regulatory interaction of CD45RBhigh and CD45RBlow CD4+ T cells may be required for protective and pathogenic immunity in EE.

scholarly journals Harnessing Antitumor CD4+ T Cells for Cancer Immunotherapy

Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 260
Author(s):  
Myriam Ben Ben Khelil ◽  
Yann Godet ◽  
Syrine Abdeljaoued ◽  
Christophe Borg ◽  
Olivier Adotévi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cancer Immunotherapy ◽  
Cd4 T Cells ◽  
Critical Role ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Cancer Therapies ◽  
The Impact

Over the past decades, CD4+ T cells have been considered as a supporting actor in the fields of cancer immunotherapy. Until recently, accumulating evidence has demonstrated the critical role of CD4+ T cells during antitumor immunity. CD4+ T cells can either suppress or promote the antitumor cytotoxic CD8+ T cell responses, either in secondary lymphoid organs or in the tumor. In this review, we provide an overview of the multifaceted role of different CD4+ T cell subsets in cancer immune response and their contribution during cancer therapies. Specifically, we focus on the latest progress regarding the impact of CD4+ T cell modulation on immunotherapies and other cancer therapies and discuss the prospect for harnessing CD4+ T cells to control tumor progression and prevent recurrence in patients.

scholarly journals A Pivotal Role for Interleukin-27 in CD8+T Cell Functions and Generation of Cytotoxic T Lymphocytes

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Noriko Morishima ◽  
Izuru Mizoguchi ◽  
Masae Okumura ◽  
Yukino Chiba ◽  
Mingli Xu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Critical Issue ◽  
Cell Functions ◽  
Antitumor Immunotherapy

Cytotoxic T lymphocytes (CTLs) play a critical role in the control of various cancers and infections, and therefore the molecular mechanisms of CTL generation are a critical issue in designing antitumor immunotherapy and vaccines which augment the development of functional and long-lasting memory CTLs. Interleukin (IL)-27, a member of the IL-6/IL-12 heterodimeric cytokine family, acts on naiveCD4+T cells and plays pivotal roles as a proinflammatory cytokine to promote the early initiation of type-1 helper differentiation and also as an antiinflammatory cytokine to limit the T cell hyperactivity and production of pro-inflammatory cytokines. Recent studies revealed that IL-27 plays an important role inCD8+T cells as well. Therefore, this article reviews current understanding of the role of IL-27 inCD8+T cell functions and generation of CTLs.

scholarly journals The role of galectin-1 in the T-lymphocytes homeostasis

2011 ◽  
Vol 10 (6) ◽  
pp. 93-99
Author(s):  
V. D. Yakushina ◽  
O. A. Vasiliyeva ◽  
N. V. Ryazantseva ◽  
V. V. Novitsky ◽  
O. Ye. Chechina ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
T Lymphocytes ◽  
Functional Ability ◽  
Cell Biology ◽  
Cell Activity ◽  
Cell Maturation ◽  
Strong Immune Response ◽  
Cell Cooperation

Fault in T-lymphocytes homeostasis leads to different diseases with poor or vise versa strong immune response. So it seems to be interesting to research molecules of T-cell cooperation to develop new more effective therapeutic methods. Important factor modulating T-cell activity is galectin-1 which takes part in multiply process of cell biology — regulation of cell maturation, migration, signal transduction, functional ability and apoptosis.

scholarly journals STAT5 and CD4+ T Cell Immunity

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 32 ◽  
Author(s):  
David L. Owen ◽  
Michael A. Farrar
Keyword(s):  
T Cell ◽  
Regulatory T Cell ◽  
Critical Role ◽  
Cell Types ◽  
T Cell Immunity ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Cell Immunity ◽  
And Function

STAT5 plays a critical role in the development and function of many cell types. Here, we review the role of STAT5 in the development of T lymphocytes in the thymus and its subsequent role in the differentiation of distinct CD4+ helper and regulatory T-cell subsets.

scholarly journals Involvement of CD26 in Differentiation and Functions of Th1 and Th17 Subpopulations of T Lymphocytes

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Xiangli Zhao ◽  
Wenhan Wang ◽  
Kai Zhang ◽  
Jingya Yang ◽  
Hendrik Fuchs ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
T Cell Activation ◽  
Solid Phase ◽  
Human Peripheral Blood ◽  
T Cell Subsets ◽  
Cd4 Cells ◽  
Ifn Γ ◽  
Cd26 Expression

CD26, acting as a costimulator of T cell activation, plays an important role in the immune system. However, the role of CD26 in the differentiation of T cell subsets, especially of new paradigms of T cells, such as Th17 and Tregs, is not fully clarified. In the present study, the role of CD26 in T cell differentiation was investigated in vitro. CD26 expression was analyzed in the different subsets of human peripheral blood T lymphocytes after solid-phase immobilized specific anti-CD3 mAb stimulation. Here, the percentage of CD4+ cells significantly increased and most of these cells were coexpressed with CD26, suggesting a close correlation of CD26 expression with the proliferation of CD4+ cells. Subsequently, after immobilized anti-CD3 mAb stimulation, CD26 high-expressing cells (CD26high) were separated from CD26 low-expressing cells (CD26low) by magnetic cell sorting. We found that the percentages of cells secreting Th1 typical cytokines (IL-2, IFN-γ) and Th17 typical cytokines (IL-6, IL-17, and IL-22) or expressing Th17 typical biomarkers (IL-23R, CD161, and CD196) in the CD26high group were markedly higher than in those in the CD26low group. In addition, a coexpression of CD26 with IL-2, IFN-γ, IL-17, IL-22, and IL-23R in lymphocytes was demonstrated by fluorescence microscopy. These results provide direct evidence that the high expression of CD26 is accompanied by the differentiation of T lymphocytes into Th1 and Th17, indicating that CD26 plays a crucial role in regulating the immune response.

T lymphocytes and Preeclampsia: The Potential Role of T cell Subsets and Related MicroRNAs in the Pathogenesis of Preeclampsia

2021 ◽  
Author(s):  
Mohammad Ali Zolfaghari ◽  
Reza Arefnezhad ◽  
Forough Parhizkar ◽  
Mohammad Saeid Hejazi ◽  
Farhad Motavalli Khiavi ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Potential Role ◽  
T Cell Subsets
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