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Helper T-Lymphocytes in Cardiovascular Diseases
Published in Shyam S. Bansal, Immune Cells, Inflammation, and Cardiovascular Diseases, 2022
Vinay Kumar, Sahil Gupta, Rachel Rosenzweig, Shyam S. Bansal
In conjunction with reduced levels, atherosclerosis is also associated with diminished immune-suppressive potential of Tregs (Figure 2.2). Peripheral Tregs isolated from the PBMCs of acute coronary syndromes (ACS) patients are significantly immunocompromised and exhibit reduced potential to inhibit immune activation when compared with Tregs from control patients54. Similarly, Tregs from ApoE−/− mice demonstrate blunted inhibition of effector T-cells when compared with Tregs from WT C57BL/6 mice53. Studies have shown that Foxp3 expression in Tregs is directly associated with their competency to inhibit immune activation, and a reduction in its expression due to either increased methylation of its gene loci59 or altered metabolism from oxidative to glycolytic60 can directly modulate Treg activity. Recently, the activation of other transcription factors, such as T-bet, with increased expression of pro-inflammatory cytokines47 or increased pro-apoptotic markers such as Bak has also been reported in Tregs61. These changes in the plasticity and phenotype of Tregs in the inflammatory milieu of atherosclerotic lesions due to the activation of T-bet gene locus and IFNγ expression ultimately result in their dysfunctional phenotype47.
Innate lymphoid cells
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
The ILC subsets react to different cues in their local environment to mount qualitatively different effector responses, depending on the type of infection or tissue injury present, which in turn dictates the orientation of the developing immune response. When a tissue is infected by intracellular microbes or viruses, or develops a tumor, stromal cells and APCs react by producing IL-12, IL-15, or IL-18. These inducer cytokines promote the differentiation of TH1 cells and ILC1s and activate their expression of the effector cytokines IFN-γ and TNFα, which in turn induce the production of oxygen radicals and cytotoxic responses by macrophages and CD8+ T cells. T-bet is the signature transcription factor of ILC1s and TH1 cells and is required for their generation.
Ustekinumab
Published in John Y. M. Koo, Ethan C. Levin, Argentina Leon, Jashin J. Wu, Alice B. Gottlieb, Moderate to Severe Psoriasis, 2014
In 1986, Mosmann and colleagues first described Th1 and Th2 cells, distinct T-cell subsets that express a unique set of cytokines and are each involved in mediating unique immune responses to differing pathogens [7]. In 2005, a third distinct T-cell subset was defined: Th17 cells [8,9]. Naïve T cells are induced to differentiate into Th1, Th2, or Th17 based upon T-cell receptor stimulation and costimulation and the specific cytokines released by antigen presenting cells [3,10]. For example, Th17 cells develop in peripheral tissue of humans after exposure to extracellular IL-1β (Figure 13.1) [11,12]. Both IL-6 and IL-23 can amplify Th17 cell differentiation but cannot substitute for IL-1β. The intracellular transcription factors RORγt and Stat3 are also critical in the development of Th17 cells from naïve T-cell precursors (Figure 13.1) [13,14]. By contrast, Th1 cells develop from naïve T cells after exposure to IL-12 and characteristically express the transcription factor T-bet [10]. Both Th17 and Th1 cells are defined at least in part by the specific set of pro-inflammatory cytokines that they produce and secrete. Th17 cells produce IL-17A (see Chapter 16), IL-17F, IL-21, IL-22, IL-6, and tumor necrosis factor-α (TNF-α), whereas Th1 cells produce IFN-γ, IL-2, and TNF-α (Figure 13.1) [3,10].
Sja-miR-71a in Schistosome egg-derived extracellular vesicles suppresses liver fibrosis caused by schistosomiasis via targeting semaphorin 4D
Published in Journal of Extracellular Vesicles, 2020
Lifu Wang, Yao Liao, Ruibing Yang, Zilong Yu, Lichao Zhang, Zifeng Zhu, Xiaoying Wu, Jia Shen, Jiahua Liu, Lian Xu, Zhongdao Wu, Xi Sun
Treg cells regulate the balance of Th1/Th2 responses in the process of S. japonicum infection [56]. Th17 has been linked with severe hepatic inflammation in schistosomiasis [57]. In addition, fibrosis is state driven by Th responses, Th2 cytokines are associated with persistent liver fibrosis in human S. japonicum infection [37,58], and Th17 can promote the proliferation and activation of stellate cells [38]. However, Treg cells can inhibit T-cell proliferation and T-effector function [39]. T-bet acts as an important transcription factor and controls Treg cell migration, homoeostasis, and function [36]. Interestingly, we observed that the percentage of T-bet+Treg cells in the livers and spleens of HBAAV2/9-Sja-miR-71a-treated S. japonicum-infected mice were increased. Thus, we concluded that Sja-miR-71a-based suppression of liver fibrosis is partly mediated by regulating the Th1/Th2/Th17/Treg balance by inhibition of Sema4D.
DNX-2401: an investigational drug for the treatment of recurrent glioblastoma
Published in Expert Opinion on Investigational Drugs, 2019
Brandon Philbrick, David C. Adamson
In addition to autophagy and oncolysis, DNX-2401 has shown to induce a local inflammatory state within the tumor that further contributes to the antitumor response induced by the adenovirus [28,37,38]. During autophagy and cell lysis of glioma tumors, damage-associated molecular patterns (DAMPs) are released and may be recognized by the innate immune system to induce an inflammatory response. It has been shown that after infection of a glioma mouse model, there is an increase in expression of the transcription factor T-bet, also known as TBX21, within the tumor (Figure 3(a)) [28]. T-bet is a transcription factor expressed by immunogenic cell lines in response to proinflammatory cytokines and has been shown to be critical in initiating a TH1 cell response [39]. Furthermore, there has been impressive increases in NK, CD4+, and CD8+ cells shortly after tumor infection with DNX-2401, further supporting that there is an induction of both an innate and acquired immune response to the therapy (Figure 3(b)) [28]. Additionally, the immunogenic markers OX40L, OX40, and IFN-γ have all been seen to be upregulated in the tumor after infection with DNX-2401 (Figure 3(c)) [28].
Decreased levels of Th17 cells are associated with invasion fungal infections after allogeneic hematopoietic stem cell transplantation
Published in Hematology, 2018
Ling Wang, Peng Zhao, Chunlei Shi, Ying Li, Ketao Lan, Mingzhe Han
Naïve CD4+T cells differentiate into numerous T cell subsets, such as Th1, Th2, Th17, and regulatory T (Treg) cells, a process regulated by specific transcription factors [7]. Among them, T-bet is a critical regulator of Th1 cell differentiation and Th1 cytokine production [8]. GATA3 is a GATA family transcription factor that controls the differentiation of naïve CD4+T cells into Th2 cells [9]. RORγt is required for the differentiation of Th17 cells and expression of IL-17 [10]. The transcription factor Foxp3 is essential for the development of Treg cells [11]. In general, Th1 and Th17 cells are considered to confer protective immunity against fungal infections, whereas Th2 and Treg cells are deleterious [12–14]. However, there has been a little explicit study about their associations with IFIs in patients after allo-HSCT.