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Extrapulmonary – Treatable traits
Published in Vibeke Backer, Peter G. Gibson, Ian D. Pavord, The Asthmas, 2023
Vibeke Backer, Peter G. Gibson, Ian D. Pavord
The underlying pathophysiological mechanism that drives CRSwNP disease is called an endotype, and type-2 inflammation is the most prominent of these. Type-2 inflammation is characterised by the presence of eosinophilic inflammation associated with type-2-related cytokines (IL4, IL5 and IL13) and circulating IgE. Nasal polyps are type-2 active; more Th2 cytokines are found in the nasal polyps than in mucosa biopsies of the inferior turbinate and bronchial tree. Further, a high level of polyp EOS in eCRS is associated with type-2 inflammatory cytokines; as high levels of IL4, IL5 and IL13 have been found in patients with eCRS; patients with mixed CRSwNP/CRSsNP may also have positive levels of type-2 cytokines, but the group with the highest level of these cytokines almost always includes patients with comorbid CRSwNP and asthma. Other cytokines, such as serum periostin, have been found in patients with severe eCRS, as well as in patients with CRSwNP and EOS in the nasal tissue, but not in those with mild or no eCRS. Blood eotaxin3, chemokine (C-C motif) and ligand 26 (CCL26) were significantly higher in patients suffering from eCRSwNP than in those without eCRSwNP, with a positive correlation between a high number of mucosal EOS and high levels of CCL26, but no correlation with other relevant cytokines. In contrast, no relationship was found between blood EOS and CCL26.
Pathophysiology of asthma
Published in Louis-Philippe Boulet, Applied Respiratory Pathophysiology, 2017
Eosinophils are considered key cells in asthma. Airway eosinophilia is mainly driven by IL-5, which promotes the production of eosinophils in the bone marrow and contributes to the recruitment of eosinophils through the influence of chemokines such as eotaxins 1, 2, and 3 (CCL11, CCL24, and CCL26, respectively); regulated upon activation, normal T cell expressed and secreted (RANTES); macrophage inflammatory protein (MIP)-1α; and arachidonic acid metabolites including cysteinyl leukotrienes and 5-keto eicosatetraenoic acid [36]. This type of cell increases in the bronchial mucosa after an allergic response. Its pro-inflammatory effects result in the liberation of cytokines, such as IL-3, IL-4, IL-5, and IL-13, various basic proteins, chemokines, growth factors, enzymes, and lipid mediators.
Lymphocyte homing and immunology of extranodal lymphoid tissues
Published in Franco Cavalli, Harald Stein, Emanuele Zucca, Extranodal Lymphomas, 2008
Mariagrazia Uguccioni, James J Campbell, Katrin Kuscher, Marshall E Kadin
Allergic insult of the lung leads to a coordinated recruitment of eosinophils. Upon such insult, lung tissue produces the cytokine interleukin-5 (IL-5), along with eotaxin chemokines, which are three closely related chemokines, CCL11,52,53 CCL24,54 and CCL26,55,56 whose only known receptor (as agonists) is CCR3. Eosinophils express CCR3 and specific receptors for IL-5, and functional blockade of either the IL-5 receptor or CCR3 inhibits eosinophil accumulation in lung.57
Targeting interleukin 4 and interleukin 13: a novel therapeutic approach in bullous pemphigoid
Published in Annals of Medicine, 2023
Fangyuan Chen, Yiman Wang, Xinyi Chen, Nan Yang, Li Li
Eosinophilia is a typical pathological feature of BP. The numbers of eosinophils and secretory granules (e.g. eosinophil cationic protein) in serum are reportedly correlated with the severity of BP [52,53]. Eosinophils can promote the pathogenesis of blistering in BP by releasing proteolytic enzymes and producing extracellular traps [35,54]. Pruritus in BP could last for months or remain the only symptom, which is difficult to control [55]. The mechanism underlying the onset of pruritus in BP may include multiple mediators, such as cytokines, chemokines, proteases, and associated receptors [56]. The study by Hashimoto et al. indicated that eosinophil is related to pruritus severity of BP [56], presumably because of chemokines activated by eosinophils. A meta-analysis revealed that numerous chemokines were elevated in BP. The levels of CCL11 (eotaxin 1), CCL17, and tumor necrosis factor-α were elevated in blister fluid, whereas CCL26 (eotaxin 3) was elevated in serum [57]. CCL11 and CCL26 are important chemokines that mediate eosinophil infiltration and degranulation. Additionally, IL-31, a Th2 cytokine primarily expressed by eosinophils in BP [58], may also contribute to pruritus in BP.
A review of current biomarkers in chronic rhinosinusitis with or without nasal polyps
Published in Expert Review of Clinical Immunology, 2023
Tsuguhisa Nakayama, Shin-Ichi Haruna
POSTN/Periostin, a matricellular protein classified under the fasciclin family, is mainly induced by IL-4 and IL-13. Periostin is highly expressed in the subepithelial regions of many chronic allergic diseases [68]. The recent studies suggests that periostin could serve as a novel biomarker reflecting type 2 inflammation in allergic diseases, particularly CRS [68]. In CRS, periostin is related to the presence of nasal polyps [69,70], tissue eosinophilia [64,71,72], IL-5 high CRSwNP [73], responsiveness to medical treatments [74], and polyp recurrence after ESS [75]. Notably, the expression level of periostin is also well recognized in control samples [69–71,75], and at the protein level, periostin is expressed at nanogram levels in normal tissues, with orders of magnitude more than other mediators [71,73], suggesting that it may be useful as a biomarker. CST1/Cystatin SN is a member of the type 2 cystatin protein family and is highly expressed in eCRSwNP. This protein plays a crucial role in activating and inducing eosinophils through various pathways [76,77]. C-C motif chemokine ligand 26 (CCL26)/eotaxin-3, which is a ligand for CCR3, is expressed on eosinophils and basophils and is produced by airway epithelium and vascular endothelial cells in response to IL-4/13 stimulation. Similar to CCL11/eotaxin-1 and CCL24/eotaxin-3, CCL26/eotaxin-3 promotes eosinophil migration and is highly expressed in eCRSwNP [65,78], type 2 CRSwNP [14], and type 2 CRSsNP [23].
Factors associated with the activity and severity of bullous pemphigoid: a review
Published in Annals of Medicine, 2020
Yangchun Liu, Yiman Wang, Xinyi Chen, Hongzhong Jin, Li Li
The level of chemokines is determined using ELISA kits. Eotaxin-1 (CCL11) and eotaxin-3 (CCL26) belong to the eotaxin subfamily of CC-chemokines, and their expression is up-regulated in the serum and blister fluid of BP patients. CCL26 is also expressed strongly in the lesions of BP patients. CCL11 and CCL26 are associated significantly with eosinophil activation, especially serum levels of CCL26, which has a close correlation with eosinophil numbers in peripheral blood. Hence, CCL26 levels could be useful for assessing BP activity, and have a role in BP development. Blockade of CCL26 function could provide a novel target for treating BP [30]. CCL11 can bind to the CCR3 expressed on eosinophils and induce eosinophil chemotaxis [31]. In addition, several observations presented that levels of eotaxin, IL-5 and CCR3 were increased in the blister fluid as well as the lesional and peri-lesional skin of BP patients. These markers also have a significant correlation with the number of dermal-infiltrating eosinophils [22,32]. There had been a pilot phase 2a study proving that bertilimumab, an anti-eotaxin-1 antibody, was safe and efficacious in the treatment of BP. This finding provided a novel target for treating BP, however, a larger controlled trial would be expected [33].