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Diagnostic tests in respiratory medicine
Published in Vibeke Backer, Peter G. Gibson, Ian D. Pavord, The Asthmas, 2023
Vibeke Backer, Peter G. Gibson, Ian D. Pavord
Asthma has long been considered a prototypical Th2-cell-mediated disease; thus, besides Th2 cells, other innate immune cells like basophils, B cells, mast cells and type-2 innate lymphoid cells (ILC2s) can produce Th2-cell-associated cytokines in asthma. The terminology has gradually shifted from ‘Th2-cell-high’ asthma to ‘type-2-high’ asthma, including both Th2 cells and ILC2s. Th2 cells are involved in producing IL4, IL5, IL10 and IL13, as well as antigen-specific IgE and IgG1. The role of ILC2s, as a source of type-2 cytokines and regulators of disease severity in human asthma, is an area of active research. Currently, IL5 and IL13 are predominant cytokines, whereas IL4 is less important. The best-known endotype of asthma is type-2-high asthma, characterised by airway and blood eosinophilia and the presence of biomarkers that depend on the type-2 cytokine IL13, such as periostin in serum and NO in exhaled breath (FeNO). Periostin and nitric oxide are both mainly produced by airway epithelial cells that express IL4Rα, and thus, respond to IL4 and/or IL13. Furthermore, TSLP is an epithelial cell–derived cytokine synthesised in response to various stimuli, an upstream alarmin, including protease allergens and microorganisms like viruses and bacteria. It is considered a master regulator of type-2 immune responses at the barrier surfaces of skin and the respiratory/gastrointestinal tract.
The Inducible Defense System: The Induction and Development of the Inducible Defence
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Michael A. Hickey, Diane Wallace Taylor
On the other hand, if Th2 cells are produced, they remain in the lymph node or spleen and interact with B cells. As shown in Figure 8.11, Th2-cell provides activation signals and cytokines that induce B cells to develop into antibody-producing plasma cells. Antibodies circulate in the blood and lymphatic fluid in search of antigen. When antibodies bind to microorganisms, they induce several effector functions. Antibodies may agglutinate the pathogens and prevent them from spreading, or block key receptors preventing their entry into host cells. Antibodies can also activate the complement cascade, which lyses the organism. The coating of the microbe makes it easier for macrophages and other phagocytic cells to destroy the microbe. If the pathogen is a virus or a foreign cell (e.g., tissue graft), cytotoxic T cells will be activated to become armed effector cells which kill the cells infected with the virus or the foreign cells. The inducible immune response may continue to develop and function in a highly coordinated fashion until the pathogen is eliminated.
Cytokines, Apoptosis, and Immune Therapy in HIV Infection
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Jerôme Estaquier, Jean-Claude Ameisen
It has been shown that Th1 and Th2 cytokines regulate the Th1/Th2 cell expansion by exerting two different effects. On one hand, cytokines such as IL-2 and IL-4 induce the expansion of the Th1 and the Th2 CD4 T cell population. On the other hand, cytokines that can be secreted by accessory cells play an indirect role in Th1 and Th2 expansion by down-regulating the converse Th cell population. The Th2 cytokine IL-10 inhibits Th1 cell expansion while the Th1 cytokine 7 interferon inhibits Th2 cell expansion [92]. Cytokine-mediated regulation of the Th1/Th2 cell ratio also operates through the control of programmed T cell death induction. Cytokine-mediated programmed Th1 cell death may represent a general mechanism of Th1 cell down-regulation (Figure 1). Among cytokines secreted by accessory cells, IL-12 and IL-10 may play an essential role in controlling the decision of CD4 Th cells to expand or to die. The local environment may fail to provide the costimulatory signals required for CD4 Th1 cell survival and lead to programmed Th1 cell death. Understanding how cytokines involved in the regulation of Th1/Th2 responses control T cell survival and T cell death may have important implications for the therapeutic approach of immunosuppression associated with chronic infectious diseases.
Long Non Coding RNA FOXD3‑AS1 Alleviates Allergic Rhinitis by Elevating the Th1/Th2 Ratio via the Regulation of Dendritic Cells
Published in Immunological Investigations, 2023
Hao Zhang, Xinhua Zhu, Hongbing Liu, Chunping Yang, Yuehui Liu
Th1/Th2 cell imbalance is the pathophysiological basis of a series of inflammatory reactions (Moss et al. 2005). After Th1 cells differentiate, the transcription factor T-bet is highly expressed, and the cytokine IFN-γ is secreted, forming a positive feedback loop; however, after Th2 cells differentiate, the transcription factor GATA-3 is highly expressed, and the cytokine IL-4 is secreted, also forming a positive feedback loop. A large number of inflammatory cells and cytokines further trigger IgE synthesis and induce allergic reactions such as basophilic granulocyte and mast cell degranulation (Lin et al. 2016). Our previous study revealed that lncRNA FOXD3-AS1 markedly inhibited Th2-type immunoreactions in CD4+ T cells cultured with LPS-treated nasal epithelial cells (NECs) (Zhang et al. 2020). Here, our work further demonstrated that LV-FOXD3-AS1 significantly reduced Th2 cells in the peripheral blood of AR model mice but had no significant effects on Th1 cells, resulting in an increase in the Th1/Th2 ratio. In addition, LV-FOXD3-AS1 also reversed the significant alterations in the levels of the Th1/Th2 cell-related cytokines IL-4, IL-5, IL-13, IL-6, and IFN-γ in the peripheral blood of AR model mice. However, the specific mechanisms by which LV-FOXD3-AS1 affected the Th1/Th2 ratio in AR model mice were not clear.
B. adolescentis ameliorates chronic colitis by regulating Treg/Th2 response and gut microbiota remodeling
Published in Gut Microbes, 2021
Lina Fan, Yadong Qi, Siwen Qu, Xueqin Chen, Aiqing Li, Maher Hendi, Chaochao Xu, Lan Wang, Tongyao Hou, Jianmin Si, Shujie Chen
Previous studies indicated that Treg suppressed colon inflammation by IL-10 secretion.7 On the other hand, Th2 cells mainly secreted IL-4 and its release in turn stimulated Th2 cell activation.22 As Treg-type cytokines IL-10, Th2-type cytokines IL-4 and IL-5 increased after B. adolescentis treatment in DSS model in our previous data, we subsequently attempted to identify the CD4+ T cell subtypes responsible for regulating colitis pathogenesis by B. adolescentis. We found that total T cells (CD4/CD3 cell: 20.3% vs.14%, p < .05) increased in B. adolescentis group fed with DSS (Supplementary Figure 2a). Moreover, compared to mice gavage with PBS, mice deal with B. adolescentis showed increased colon lamina propria Th2 cells (Th2/CD4 T cells: 4.32% vs.2.28%, p < .001) (Figure 5b) and Treg cells (Treg/CD4 T cells: 45.6% vs.34.8%, p < .05) (Figure 5d). In the while, we found other helper T cells Th1 and Th17 cells showed no significant diffidence in B. adolescentis group and PBS group fed with DSS (Figure 5a,c).
Chronic rhinosinusitis with nasal polyps: mechanistic insights from targeting IL-4 and IL-13 via IL-4Rα inhibition with dupilumab
Published in Expert Review of Clinical Immunology, 2020
The exact inflammatory and remodeling pathways modulated by dupilumab in CRSwNP are currently uncertain. It is possible nevertheless to begin to propose a mechanistic model (Figure 4). The basic assumptions are as follows. The establishment of Th2 cell lineage and cell survival is progressively down regulated. As a consequence, tissue Th2 cell numbers decrease. IL-4 no longer inhibits iTreg generation. As such, immune regulation is restored. This combined with loss of T2 inflammatory cytokine expression decreases the sinonasal mucosal cytokine inflammatory burden. As such, tissue inflammatory cell numbers such as that of Th2 cells, eosinophils, mast cells and basophils as examples decrease. B cell drive is lost, and thence less functional IgE and pro-inflammatory IgG production occurs. Knock down in IgE and thus IgE mediated inflammatory pathways are particularly important. Studies with the anti-IgE biologic omalizumab both in real life and Phase 3 replicate studies have recently confirmed rapid clinical response with decrease in NPS and improvement in nasal symptoms [98,99]. IgE-FcεRI mediated mast cell and basophil activity, and subsequent activation of downstream inflammatory cascades is thereby diminished. Immune amplification mechanisms and auto-inflammatory loops become down-regulated.