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Immune Responses
Published in Ronald Fayer, Lihua Xiao, Cryptosporidium and Cryptosporidiosis, 2007
IL-13 has overlapping functions with IL-4, and the two cytokines employ the same receptor, IL-4Ra (Wynn, 2003). BALB/c IL-4Ra1 mice, like the IL-41 mice, were found to have more intense C. parvum infection than wild-type mice and the rate of recovery was initially slower than in IL-41 mice (McDonald et al., 2004). This suggests, therefore, that IL-13 may have a protective role in this mouse strain. IL-13, unlike IL-4, did not increase the capacity of IFN-? to inhibit C. parvum reproduction in an enterocyte cell line, however (Lean et al., 2003). Malnourished Haitian children with persistent cryptosporidiosis were found to have a marked intestinal inflammatory response and expressed IL-13 but not IFN-? (Kirkpatrick et al., 2002), which does not signify a protective role for the cytokine.
Biomedical Applications III: Delivery of Immunostimulants and Vaccines
Published in Giorgia Pastorin, carbon nanotubes, 2019
Jian Li, Venkatesan Gopalakrishnan, Pastorin Giorgia
Once a B cell encounters a pathogen (antigen), it processes and presents the same antigen (although not in the native shape but in a digested form, i.e., as a peptide fragment) to special subtypes of T cells (called Th cells or helper T cells, i.e., CD4+ T cells) through a class IIMHC, thus acting as antigen- presenting cells (APCs). This phenomenon, known as immunological synapse, stimulates CD4+ T cells to secrete cytokines2 that activate specific B cells towards the production of antibodies against the antigens. Type 1 T helper (Thl) cells produce interferon-gamma (IFN-γ), interleukin (IL)-2 and tumour necrosis factor (TNF)-ß, which activate macrophages and are responsible for cell-mediated immunity and phagocyte-dependent protective responses. By contrast, type 2 Th (Th2) cells produce interleukin (IL)-4, IL-5, IL-10 and IL-13, which are responsible for strong antibody production, eosinophil activation and inhibition of several macrophage functions, thus providing phagocyte- independent protective responses. Thl cells mainly develop after infection by intracellular bacteria and some viruses, whereas Th2 cells predominate in response to infestations by gastrointestinal nematodes.3 Once stimulated by Th cells, activated B cells produce antibodies (e.g., IgG, IgA or IgE),4 which assist in inhibiting extraneous pathogens and neutralising viruses and bacterial toxins. Alternatively, cytotoxic CD8+ (CTL) T cells can directly clear virus-infected cells and regulate the immune responses to foreign antigens on the basis of the cytokine profile they secrete via a different mechanism.
Pro- and Anti-Inflammatory Cytokine Signaling within 3D Tissue Models
Published in Karen J.L. Burg, Didier Dréau, Timothy Burg, Engineering 3D Tissue Test Systems, 2017
Stephen L. Rego, Tian McCann, Didier Dréau
IL4 is an anti-inflammatory cytokine expressed by NK cells, basophils, and specific subsets of T cells (Chatterjee et al. 2014). IL4 stimulates T and B cell proliferation and differentiation and can induce macrophages to express an alternative phenotype that promotes wound healing functions (Chatterjee et al. 2014). The receptor for IL4, IL4Rα, exists in three distinct forms throughout the body and can be activated by both IL4 and IL13, all having similar biologic functions (Ito et al. 2009; Andrews et al. 2013).
Genetic variants affecting chemical mediated skin immunotoxicity
Published in Journal of Toxicology and Environmental Health, Part B, 2022
Isisdoris Rodrigues de Souza, Patrícia Savio de Araujo-Souza, Daniela Morais Leme
Loss of FLG function is also related to an enhanced activation of group 2 innate lymphoid cells (ILC2) – cells associated with AD progression. ILC2 express MHC II on their cell surface and secrete IL-5 and IL-13 (effector type 2 cytokines) in response to epithelial cell-derived cytokines IL-25, IL-33 and/or thymic stromal lymphopoietin (TSLP). ILC2 also respond to mast cell mediators, such as prostaglandin D2 (PGD2), resulting in ILC2 migration, production of type 2 cytokines and upregulation of IL-33 and IL-25 receptor subunits expression (ST2 and IL-17RA) (Xue et al. 2014). ILC2-derived cytokines, such as IL-13, are necessary to activate and expand DCs, demonstrating the critical role of ILC2 in Th2 response (Rafei-Shamsabadi et al. 2019).
Topical application of celastrol alleviates atopic dermatitis symptoms mediated through the regulation of thymic stromal lymphopoietin and group 2 innate lymphoid cells
Published in Journal of Toxicology and Environmental Health, Part A, 2021
Jae Kwon Lee, Jin Kyung Seok, Ilyoung Cho, Gabsik Yang, Kyu-Bong Kim, Seung Jun Kwack, Han Chang Kang, Yong-Yeon Cho, Hye Suk Lee, Joo Young Lee
Thymic stromal lymphopoietin (TSLP) is expressed by dermal epithelial cells that stimulate Th2 differentiation to initiate Th2 immune responses (He et al. 2008). The expression of TSLP is involved in the pathogenesis of various diseases including atopic dermatitis, asthma, and inflammatory arthritis (Ebner et al. 2007; Yang et al. 2018; Ying et al. 2005). TSLP expression levels are up-regulated in atopic dermatitis patients skin lesions (Soumelis et al. 2002). In atopic dermatitis, TSLP is produced by skin keratinocytes in response to external stimuli such as allergens, cytokines, viruses, bacteria and fungi, and plays an important role in early development of diseases (Ziegler 2012). Increased TSLP levels stimulate immature dendritic cells to express OX40 ligand in an antigen-specific manner (Gilliet et al. 2003). The expression of OX40 ligand-dendritic cells promotes the differentiation of naïve CD4 T cells into Th2 cells (Ohshima et al. 1997). TSLP also directly stimulates development of naïve CD4 T cells or CD8 T cells into Th2 cells. The activation of TSLP receptor (TSLPR) initiates IL-4 gene transcription, which induces positive feedback to upregulate the TSLPR located on CD4 T cells (Omori and Ziegler 2007). It is noteworthy that Th2 cells produce increased Th2 cytokines levels of IL-4, IL-5, and IL-13 (Leyva-Castillo et al. 2013). Th2 cytokines lead to elevated IgE production by inducing class switching in B cells, and skin inflammatory responses, exacerbating skin barrier defects in atopic dermatitis (Guttman-Yassky and Krueger 2017). Therefore, TSLP expression is considered a hallmark of early pathogenesis of atopic dermatitis (Wang et al. 2013).
Nanomaterial-induced toxicity in pathophysiological models representative of individuals with pre-existing medical conditions
Published in Journal of Toxicology and Environmental Health, Part B, 2023
Sreejesh Sreedharan, Georgios Zouganelis, Samantha J Drake, Gyanendra Tripathi, Ali Kermanizadeh
With an aging global population, chronic respiratory diseases are becoming a prominent cause of death and disability. This trend has been increasing for over a decade with the recent COVID-19 pandemic likely to add to this further (Ekezie et al. 2021). Among the range of respiratory diseases, COPD and asthma have the highest prevalence. In 2017, there were 3.2 million deaths attributed to COPD and 495,000 deaths to asthma. In the same year, the incident cases of chronic respiratory diseases were estimated at 300 million mostly due to asthma (69%) and COPD (29%) (WHO 2022). Asthma is categorized by airway hyperresponsiveness, inflammation and overproduction of mucus all of which contribute to the obstruction of the airways resulting in characteristic symptoms associated with the disease (Krishnan et al. 2012). Although different variants of asthma have been identified allergic asthma is the most well investigated. The current understanding of the allergic variant of disease is uptake of the allergen by pulmonary dendritic cells (specialized antigen presenting cells), which subsequently process and present the antigen to T helper cells. This results in activation of different naive lymphocytes in Th2 type cells. Th2 cells then stimulate humoral immune response promoting B cell proliferation and production of IL4 and IL13. The activated B lymphocytes produce antigen specific IgE, which binds to the allergen and receptors on mast cells resulting in their degranulation and release of histamine, leukotrienes leading to further inflammation. Allergic asthma is also characterized by an influx of innate immune cells in response to the allergen amongst which eosinophils, macrophages and neutrophil are the most important (Leblond et al. 2009). Finally, epithelial cells (inflammatory cytokine secretion), smooth muscle cells (hypertrophy and hyperplasia) and fibroblasts (collagen deposition) are all involved in progression of disease and symptoms (Kudo, Ishigatsubo, and Aoki 2013)