nach oben

Erschienen in:

26.11.2021 | Original Article

The Emerging Roles of T Helper Cell Subsets and Cytokines in Severe Neutrophilic Asthma

verfasst von: Qi Chen, Siji Nian, Yingchun Ye, Dan Liu, Hong Yu, Hong Xiong, Bi Pan, Lu Xiao, Chunrong Fan, Qing Yuan

Erschienen in: Inflammation | Ausgabe 3/2022

Einloggen, um Zugang zu erhalten

Abstract—

Neutrophilic asthma (NA) is a severe type of steroid resistant asthma, and so far the immune mechanisms underlying NA are not clear. In this article, we performed a comprehensive assessment of Th-cell subsets and cytokines in severe NA patients. A total of 13 healthy individuals and 31 severe asthma patients were enrolled in this study. Refractory asthma patients were defined as those with eosinophilic asthma (EA, accounted for 32% of asthmatic patients) or NA (68%) according to sputum neutrophil/eosinophil counts or blood eosinophils. Th-cell subsets in peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry, and cytokines were detected by cytometric bead array (CBA). The results showed significant differences were observed in Th-cell phenotypes, where the number of Th1 cells were reduced and the numbers of Th2 cells were increased in NA and EA groups, respectively, when compared with healthy controls. Th17 cells were not strongly associated with severe neutrophilic asthma. The frequencies of mucosal-associated invariant T (MAIT) cells were strikingly reduced in severe asthma patients, especially in the NA group. This NA group also showed increased levels of IL-17A, IL-17F, TNF-α, and IL-6 in serum and increased levels of IL-17A, IL-17F, IFN-γ, TNF-α, IL-1β, IL-5, IL-6, and IL-8 in sputum. In addition, sputum IL-6 was positively correlated with TNF-α, IFN-γ, IL-17A, and IL-8. Our results uncovered a controversial role for Th17 cells, which were reduced in severe asthma patients. Severe neutrophilic asthma was associated with a striking deficiency of MAIT cells and high pro-inflammatory cytokine levels.

Nur mit Berechtigung zugänglich

Park, H.S., M.K. Kim, N. Imai, T. Nakanishi, M. Adachi, K. Ohta, et al. 2016. A phase 2a study of benralizumab for patients with eosinophilic asthma in South Korea and Japan. International Archives of Allergy and Immunology 169 (3): 135–145. https://doi.org/10.1159/000444799.CrossRefPubMed

Akdis, M., J. Verhagen, A. Taylor, F. Karamloo, C. Karagiannidis, R. Crameri, et al. 2004. Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. Journal of Experimental Medicine 199 (11): 1567–1575. https://doi.org/10.1084/jem.20032058.CrossRefPubMedCentral

Katz, L.E., G.J. Gleich, B.F. Hartley, S.W. Yancey, and H.G. Ortega. 2014. Blood eosinophil count is a useful biomarker to identify patients with severe eosinophilic asthma. Annals of the American Thoracic Society 11 (4): 531–536. https://doi.org/10.1513/AnnalsATS.201310-354OC.CrossRefPubMed

Ordoñez, C.L., T.E. Shaughnessy, M.A. Matthay, and J.V. Fahy. 2000. Increased neutrophil numbers and IL-8 levels in airway secretions in acute severe asthma: Clinical and biologic significance. American Journal of Respiratory and Critical Care Medicine 161: 1185–1190. https://doi.org/10.1164/ajrccm.161.4.9812061.CrossRefPubMed

Guiddir, T., P. Saint-Pierre, E. Purenne-Denis, N. Lambert, Y. Laoudi, R. Couderc, et al. 2017. Neutrophilic steroid-refractory recurrent wheeze and eosinophilic steroid-refractory asthma in children. The Journal of Allergy and Clinical Immunology: In Practice 5 (5): 1351–1361. https://doi.org/10.1016/j.jaip.2017.02.003.

Green, R.H., C.E. Brightling, G. Woltmann, D. Parker, A.J. Wardlaw, and I.D. Pavord. 2002. Analysis of induced sputum in adults with asthma: Identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids. Thorax 57 (10): 875–879. https://doi.org/10.1136/thorax.57.10.875.CrossRefPubMedPubMedCentral

Sur, S., T.B. Crotty, G.M. Kephart, B.A. Hyma, T.V. Colby, C.E. Reed, et al. 1993. Sudden-onset fatal asthma A distinct entity with few eosinophils and relatively more neutrophils in the airway submucosa? American Review of Respiratory Disease 148 (3): 713–719. https://doi.org/10.1164/ajrccm/148.3.713.CrossRef

Simpson, J.L., R. Scott, M.J. Boyle, and P.G. Gibson. 2006. Inflammatory subtypes in asthma: Assessment and identification using induced sputum. Respirology 11 (1): 54–61. https://doi.org/10.1111/j.1440-1843.2006.00784.x.CrossRefPubMed

Gibson, P.G. 2009. Inflammatory phenotypes in adult asthma: Clinical applications. The Clinical Respiratory Journal 3 (4): 198–206. https://doi.org/10.1111/j.1752-699X.2009.00162.x.CrossRefPubMed

10.

McGovern, T.K., M. Goldberger, B. Alard, S. Farahnak, Y. Hamamoto, M. O’Sullivan, et al. 2015. Neutrophils Mediate airway hyperresponsiveness after chlorine-induced airway injury in the mouse. American Journal of Respiratory Cell and Molecular Biology 52 (4): 513–522. https://doi.org/10.1165/rcmb.2013-0430OC.CrossRefPubMed

11.

Barczyk, A., W. Pierzcha, and E. Sozañska. 2003. Interleukin-17 in sputum correlates with airway hyperresponsiveness to methacholine. Respiratory Medicine 97 (6): 726–733. https://doi.org/10.1053/rmed.2003.1507.CrossRefPubMed

12.

Matangkasombut, P., G. Marigowda, A. Ervine, L. Idris, M. Pichavant, H.Y. Kim, et al. 2009. Natural killer T cells in the lungs of patients with asthma. Journal of Allergy and Clinical Immunology 123 (5): 1181–1185. https://doi.org/10.1016/j.jaci.2009.02.013.CrossRef

13.

Chenuet, P., L. Fauconnier, F. Madouri, T. Marchiol, N. Rouxel, A. Aur´, et al. 2017. Neutralization of either IL-17A or IL-17F is sufficient to inhibit house dust mite induced allergic asthma in mice. Clinical Science 131 (20): 2533–2548. https://doi.org/10.1042/CS20171034.CrossRefPubMed

14.

Jia, A., Y. Wang, W. Sun, B. Xiao, Y. Wei, L. Qiu, et al. 2017. MBD2 regulates Th17 cell differentiation and experimental severe asthma by affecting IRF4 expression. Mediators of Inflammation 2017: 6249685. https://doi.org/10.1155/2017/6249685.CrossRefPubMedPubMedCentral

15.

Liu, W., S. Liu, M. Verma, I. Zafar, J.T. Good, D. Rollins, et al. 2016. Mechanism of TH2/TH17-predominant and neutrophilic TH2/TH17-low subtypes of asthma. Journal of Allergy and Clinical Immunology 139: 1548–1558. https://doi.org/10.1016/j.jaci.2016.08.032.CrossRef

16.

Durrant, D.M., and D.W. Metzger. 2010. Emerging roles of T helper subsets in the pathogenesis of asthma. Immunological Investigations 39 (4–5): 526–549. https://doi.org/10.3109/08820131003615498.CrossRefPubMedPubMedCentral

17.

Agarwal, A., M. Singh, B.P. Chatterjee, A. Chauhan, and A. Chakraborti. 2014. Interplay of T helper 17 cells with CD4(+)CD25(high) FOXP3(+) Tregs in regulation of allergic asthma in pediatric patients. International journal of pediatrics 2014: 636238. https://doi.org/10.1155/2014/636238.CrossRefPubMedPubMedCentral

18.

Yang, X., J.-H. Zhang, W.-S. Deng, and C.-Q. Li. 2018. Imbalance of γδT17/γδTreg cells in the pathogenesis of allergic asthma induced by ovalbumin. Brazilian Journal of Medical and Biological Research 51: e7127–e7127. https://doi.org/10.1590/1414-431X20187127.CrossRefPubMedPubMedCentral

19.

Toubal, A., I. Nel, S. Lotersztajn, and A. Lehuen. 2019. Mucosal-associated invariant T cells and disease. Nature Reviews Immunology 19 (10): 643–657. https://doi.org/10.1038/s41577-019-0191-y.CrossRefPubMed

20.

Kjer-Nielsen, L., O. Patel, A.J. Corbett, J. Le Nours, B. Meehan, L. Liu, et al. 2012. MR1 presents microbial vitamin B metabolites to MAIT cells. Nature 491: 717–723. https://doi.org/10.1038/nature11605.CrossRefPubMed

21.

Le Bourhis, L., E. Martin, I. Péguillet, A. Guihot, N. Froux, M. Coré, et al. 2010. Antimicrobial activity of mucosal-associated invariant T cells. Nature Immunology 11 (8): 701–708. https://doi.org/10.1038/ni.1890.CrossRefPubMed

22.

Hartmann, N., M.J. Harriff, C.P. McMurtrey, W.H. Hildebrand, D.M. Lewinsohn, and M. Kronenberg. 2018. Role of MAIT cells in pulmonary bacterial infection. Molecular immunology 101: 155–159. https://doi.org/10.1016/j.molimm.2018.06.270.CrossRefPubMedPubMedCentral

23.

Hinks, T.S.C., X. Zhou, K.J. Staples, B.D. Dimitrov, A. Manta, T. Petrossian, et al. 2015. Innate and adaptive T cells in asthmatic patients: Relationship to severity and disease mechanisms. Journal of Allergy and Clinical Immunology 136 (2): 323–333. https://doi.org/10.1016/j.jaci.2015.01.014.CrossRef

24.

Chipps, B.E. 2006. Asthma as a risk factor for invasive pneumococcal disease. Pediatrics 352 (20): 2082–2090. https://doi.org/10.1542/peds.2006-0900fff.CrossRef

25.

Green, B.J., S. Wiriyachaiporn, C. Grainge, G.B. Rogers, V. Kehagia, et al. 2014. Potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma. PLoS ONE 9 (6): e100645. https://doi.org/10.1371/journal.pone.0100645.CrossRefPubMedPubMedCentral

26.

Jevnikar, Z., J. Östling, E. Ax, J. Calvén, K. Thörn, E. Israelsson, et al. 2019. Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation. Journal of Allergy and Clinical Immunology 143 (2): 577–590. https://doi.org/10.1016/j.jaci.CrossRef

27.

Gordon, J.R., and S.J. Galli. 1990. Mast cells as a source of both preformed and immunologically inducible TNF-α/cachectin. Nature 346 (6281): 274–276. https://doi.org/10.1038/346274a0.CrossRefPubMed

28.

Ayuk, A.C., A. Ubesie, C.L. Odimegwu, and K. Iloh. 2017. Use of Global initiative for asthma (GINA) guidelines in asthma management among paediatric residents in a Sub Saharan African country: A cross-sectional descriptive study. The Pan African Medical Journal 27: 120. https://doi.org/10.11604/pamj.2017.27.120.9260.

29.

Gibson, P.G., J.W. Wlodarczyk, M.J. Hensley, M. Gleeson, R.L. Henry, A.W. Cripps, et al. 1998. Epidemiological association of airway inflammation with asthma symptoms and airway hyperresponsiveness in childhood. American Journal of Respiratory and Critical Care Medicine 158 (1): 36–41. https://doi.org/10.1164/ajrccm.158.1.9705031.CrossRefPubMed

30.

Javadian, A., E. Salehi, K. Bidad, M.A. Sahraian, and M. Izad. 2014. Effect of estrogen on Th1 Th2 and Th17 cytokines production by proteolipid protein and pha activated peripheral blood mononuclear cells isolated from multiple sclerosis patients. Archives of Medical Research 45 (2): 177–182. https://doi.org/10.1016/j.arcmed.2014.01.002.CrossRefPubMed

31.

Elson, L.H., T.B. Nutman, D.D. Metcalfe, and C. Prussin. 1995. Flow cytometric analysis for cytokine production identifies T helper 1 T helper 2 and T helper 0 cells within the human CD4+CD27- lymphocyte subpopulation. The Journal of Immunology 154 (9): 4294–4301.PubMed

32.

Choy, D.F., K.M. Hart, L.A. Borthwick, A. Shikotra, D.R. Nagarkar, S. Siddiqui, et al. 2015. TH2 and TH17 inflammatory pathways are reciprocally regulated in asthma. Science Translational Medicine 7 (301): 301ra129. https://doi.org/10.1126/scitranslmed.aab3142.

33.

Wood, L.G., K.J. Baines, J. Fu, H.A. Scott, and P.G. Gibson. 2012. The neutrophilic inflammatory phenotype is associated with systemic inflammation in asthma. Chest 142 (1): 86–93. https://doi.org/10.1378/chest.11-1838.CrossRefPubMed

34.

Espinosa-Carrasco, G., C. Le Saout, P. Fontanaud, T. Stratmann, P. Mollard, M. Schaeffer, et al. 2018. CD4+T helper cells play a key role in maintaining diabetogenic CD8+T cell function in the pancreas. Frontiers in Immunology 8: 2001. https://doi.org/10.3389/fimmu.2017.02001.CrossRefPubMedPubMedCentral

35.

Wu, H.Y., E.M. Center, G.C. Tsokos, and H.L. Weiner. 2009. Suppression of murine SLE by oral anti-CD3: Inducible CD4+CD25-LAP+ regulatory T cells control the expansion of IL-17+ follicular helper T cells. Lupus 18 (7): 586–596. https://doi.org/10.1177/0961203308100511.CrossRefPubMedPubMedCentral

36.

Zhang, Y., Y. Li, T.T. Lv, Z.J. Yin, and X.B. Wang. 2015. Elevated circulating Th17 and follicular helper CD4⁺ T cells in patients with rheumatoid arthritis. APMIS 123 (8): 659–666. https://doi.org/10.1111/apm.12399.CrossRefPubMed

37.

Lu, Y., H. Kared, S.W. Tan, E. Becht, E.W. Newell, H.P.S. Van Bever, et al. 2018. Dynamics of helper CD4 T cells during acute and stable allergic asthma. Mucosal Immunology 11 (6): 1640–1652. https://doi.org/10.1038/s41385-018-0057-9.CrossRefPubMed

38.

Bui, T.T., C.H. Song, O.H. Chai, H.S. Shin, C.-H. Lee, C.H. Piao, et al. 2017. Citrus tachibana leaves ethanol extract alleviates airway inflammation by the modulation of Th1/Th2 imbalance via inhibiting NF-κ B signaling and histamine secretion in a mouse model of allergic asthma. Journal of medicinal food 20 (7): 676–684. https://doi.org/10.1089/jmf.2016.3853.CrossRefPubMed

39.

Zhu, M., Z. Liang, T. Wang, R. Chen, G. Wang, and Y. Ji. 2016. Th1/Th2/Th17 cells imbalance in patients with asthma with and without psychological symptoms. Allergy & Asthma Proceedings 37 (2): 148–156. https://doi.org/10.2500/aap.2016.37.3928.CrossRef

40.

Ji, N.F., Y.C. Xie, M.S. Zhang, X. Zhao, H. Cheng, H. Wang, et al. 2014. Ligustrazine corrects Th1/Th2 and Treg/Th17 imbalance in a mouse asthma model. International Immunopharmacology 21 (1): 76–81. https://doi.org/10.1016/j.intimp.2014.04.015.CrossRefPubMed

41.

Bochner, B.S., B.J. Undem, and L.M. Lichtenstein. 1994. Immunological aspects of allergic asthma. Annual Review of Immunology 12: 295–335. https://doi.org/10.1146/annurev.iy.12.040194.001455.CrossRefPubMed

42.

Kursawe, N., J. Jäger, S. Reinhardt, A. Willing, and M.A. Friese. 2018. Production of IL-17 by MAIT cells is increased in multiple sclerosis and is associated with IL-7 receptor expression. The Journal of Immunology 200 (3): 974–982. https://doi.org/10.4049/jimmunol.1701213.CrossRefPubMed

43.

Atif, M., S. Warner, and Y.H. Oo. 2018. Linking the gut and liver: Crosstalk between regulatory T cells and mucosa-associated invariant T cells. Hepatology International 12 (4): 305–314. https://doi.org/10.1007/s12072-018-9882-x.CrossRefPubMed

44.

Beudeker, B.J.B., G.W. van Oord, J.E. Arends, J. Schulze zur Wiesch, M.S. van der Heide, R.J. de Knegt, et al. 2018. Mucosal-associated invariant T-cell frequencies and function in blood and liver of HCV mono- and HCV/HIV co-infected patients with advanced fibrosis. Liver International 38 (3): 458–468. https://doi.org/10.1111/liv.13544.CrossRefPubMed

45.

Jo, Y.G., H.J. Choi, J.C. Kim, Y.N. Cho, J.H. Kang, H.M. Jin, et al. 2017. Deficiencies of circulating mucosal-associated invariant T cells and natural killer T cells in patients with multiple trauma. Journal of Korean Medical Science 32: 750–756. https://doi.org/10.3346/jkms.2017.32.5.750.CrossRefPubMedPubMedCentral

46.

Khaitan, A., M. Kilberg, A. Kravietz, T. Ilmet, C. Tastan, M. Mwamzuka, et al. 2016. HIV-infected children have lower frequencies of CD8+ mucosal-associated invariant T (MAIT) cells that correlate with innate Th17 and Th22 cell subsets. PLoS ONE 11 (8): e0161786. https://doi.org/10.1371/journal.pone.0161786.CrossRefPubMedPubMedCentral

47.

Gavino, A.C., K. Nahmod, U. Bharadwaj, G. Makedonas, and D.J. Tweardy. 2016. STAT3 inhibition prevents lung inflammation, remodeling, and accumulation of Th2 and Th17 cells in a murine asthma model. Allergy 71 (12): 1684–1692. https://doi.org/10.1111/all.12937.CrossRefPubMed

48.

Hinks, T., X. Zhou, K. Staples, B. Dimitrov, A. Manta, T. Petrossian, et al. 2015. Multidimensional endotypes of asthma: Topological data analysis of cross-sectional clinical pathological and immunological data. The Lancet 385 (Suppl 1): S42. https://doi.org/10.1016/S0140-6736(15)60357-9.CrossRef

49.

Ricciardolo, F.L.M., V. Sorbello, A. Folino, F. Gallo, G.M. Massaglia, et al. 2017. Identification of IL-17F/frequent exacerbator endotype in asthma. Journal of Allergy and Clinical Immunology 140 (2): 395–406. https://doi.org/10.1016/j.jaci.2016.CrossRef

50.

Sorbello, V., G. Ciprandi, A. Di Stefano, G.M. Massaglia, G. Favatà, S. Conticello, et al. 2015. Nasal IL-17F is related to bronchial IL-17F/neutrophilia and exacerbations in stable atopic severe asthma. Allergy 70 (2): 236–240. https://doi.org/10.1111/all.12547.CrossRefPubMed

51.

Chang, Y., L. Al-Alwan, P.A. Risse, L. Roussel, S. Rousseau, A.J. Halayko, et al. 2011. TH17 cytokines induce human airway smooth muscle cell migration. Journal of Allergy and Clinical Immunology 127 (4): 1046–1053. https://doi.org/10.1016/j.jaci.2010.12.1117.CrossRef

52.

Honda, K., H. Wada, M. Nakamura, K. Nakamoto, T. Inui, M. Sada, et al. 2016. IL-17A synergistically stimulates TNF-α-induced IL-8 production in human airway epithelial cells: A potential role in amplifying airway inflammation. Experimental Lung Research 42 (4): 205–216. https://doi.org/10.1080/01902148.2016.1190796.CrossRefPubMed

53.

Kim, Y.M., H. Kim, S. Lee, S. Kim, J.-U. Lee, Y. Choi, et al. 2020. Airway G-CSF identifies neutrophilic inflammation and contributes to asthma progression. European Respiratory Journal 55 (2): 1900827. https://doi.org/10.1183/13993003.00827-2019.CrossRef

54.

Irvin, C., I. Zafar, J. Good, D. Rollins, C. Christianson, M.M. Gorska, et al. 2014. Increased frequencies of dual-positive TH2/TH17 cells in bronchoalveolar lavage fluid characterizes a population of patients with severe asthma. Journal of Allergy and Clinical Immunology 134 (5): 1175–1186. https://doi.org/10.1016/j.jaci.2014.05.038.CrossRef

55.

Niu, Q., Z. Huang, X. Wu, Y. Jin, Y. An, Y. Li, et al. 2018. Enhanced IL-6/phosphorylated STAT3 signaling is related to the imbalance of circulating T follicular helper/T follicular regulatory cells in patients with rheumatoid arthritis. Arthritis Research & Therapy 20 (1): 200. https://doi.org/10.1186/s13075-018-1690-0.CrossRef

56.

Harintho, M.T., D.C.N. Baker, J.Y. Cephus, K. Goleniewska, and R. Stokes Peebles Jr. 2014. IL-4 signaling attenuates γδT cell IL-17A protein expression. Journal of Allergy and Clinical Immunology 133: AB248. https://doi.org/10.1016/j.jaci.2013.12.883.

57.

Lezmi, G., R. Abou-Taam, N. Garcelon, C. Dietrich, F. Machavoine, C. Delacourt, et al. 2019. Evidence for a MAIT-17-high phenotype in children with severe asthma. Journal of Allergy and Clinical Immunology 144: 1714–1716. https://doi.org/10.1016/j.jaci.2019.08.003.CrossRef

58.

Ullah, M.A., J.A. Revez, Z. Loh, J. Simpson, V. Zhang, L. Bain, et al. 2015. Allergen-induced IL-6 trans-signaling activates γδ T cells to promote type 2 and type 17 airway inflammation. Journal of Allergy and Clinical Immunology 136 (4): 1065–1073. https://doi.org/10.1016/j.jaci.2015.02.032.CrossRef

59.

Nieto Fontarigo, J.J., F.J. Salgado, M.E. San José, M. Cruz, L. Valdés, A. Pérez Díaz, et al. 2019. Expansion of different subpopulations of CD26−/low T cells in allergic and non-allergic asthmatics. Scientific Reports 9 (1): 7556. https://doi.org/10.1038/s41598-019-43622-8.CrossRefPubMedPubMedCentral

60.

Bozek, A., B. Rogala, J. Gluck, and J. Jarzab. 2015. Prevalence of IgE-mediated allergy and evaluation of Th1/Th2 cytokine profiles in patients with severe bronchial asthma. Postȩpy Dermatologii i Alergologii 32 (4): 274–280. https://doi.org/10.5114/pdia.2015.53323.CrossRefPubMedPubMedCentral

61.

Hu, C., Z. Li, J. Feng, Y. Tang, L. Qin, X. Hu, et al. 2018. Glucocorticoids modulate Th1 and Th2 responses in asthmatic mouse models by inhibition of Notch1 signaling. International Archives of Allergy and Immunology 175 (1–2): 44–52. https://doi.org/10.1159/000485890.CrossRefPubMed

62.

Zhou, M., Z. Cui, X. Guo, L. Ren, M. Yang, Z. Fan, et al. 2015. Blockade of Notch signalling by γ-secretase inhibitor in lung T cells of asthmatic mice affects T cell differentiation and pulmonary inflammation. Inflammation 38 (3): 1281–1288. https://doi.org/10.1007/s10753-014-0098-5.CrossRefPubMed

63.

Bossley, C.J., L. Fleming, A. Gupta, N. Regamey, J. Frith, T. Oates, L. Tsartsali, et al. 2012. Pediatric severe asthma is characterized by eosinophilia and remodeling without TH2 cytokines. Journal of Allergy and Clinical Immunology 129 (4): 974–982. https://doi.org/10.1016/j.jaci.2012.01.059.CrossRef

64.

Cottrez, F., S.D. Hurst, R.L. Coffman, and H. Groux. 2014. T regulatory cells 1 inhibit a Th2-specific response in vivo. The Journal of Immunology 165 (9): 4848–4853. https://doi.org/10.4049/jimmunol.165.9.4848.CrossRef

65.

Hoseini-Shahrestanak, S., N. Bazargan, L. Rahimian, M. Nemati, S. Solaymani, and A. Jafarzadeh. 2018. Imbalanced expression of Th2 and Treg cell-related parameters in peripheral blood mononuclear cells in patients with allergic asthma. Tanaffos 17: 1–12.PubMedPubMedCentral

66.

Li, C., A. Sheng, X. Jia, Z. Zeng, X. Zhang, W. Zhao, et al. 2018. Th17/Treg dysregulation in allergic asthmatic children is associated with elevated notch expression. Journal of Asthma 55 (1): 1–7. https://doi.org/10.1080/02770903.2016.1266494.CrossRef

67.

Bacchetta, R., E. Gambineri, and M.G. Roncarolo. 2007. Role of regulatory T cells and FOXP3 in human diseases. Journal of Allergy and Clinical Immunology 120 (2): 227–235. https://doi.org/10.1016/j.jaci.2007.06.023.CrossRef

68.

Pasare, C., and R. Medzhitov. 2003. Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science 299 (5609): 1033–1036. https://doi.org/10.1126/science.1078231.CrossRefPubMed

69.

Sobkowiak, P., I. Wojsyk-Banaszak, M. Kowalewska, E. Wasilewska, W. Langwiński, Z. Kycler, et al. 2017. Interleukin 1β polymorphism and serum level are associated with pediatric asthma. Pediatric Pulmonology 52 (12): 1565–1571. https://doi.org/10.1002/ppul.23893.CrossRefPubMed

70.

Kim, R.Y., J.W. Pinkerton, A.T. Essilfie, A.A.B. Robertson, K.J. Baines, A.C. Brown, et al. 2017. Role for NLRP3 inflammasome-mediated IL-1β-dependent responses in severe steroid-resistant asthma. American Journal of Respiratory and Critical Care Medicine 196 (3): 283–297. https://doi.org/10.1164/rccm.201609-1830OC.CrossRefPubMed

71.

Esnault, S., and J.S. Malter. 2002. GM-CSF regulation in eosinophils. Archivum Immunologiae Et Therapiae Experimentalis 50 (2): 121–130.PubMed

72.

Kishimoto, T. 2010. IL-6: From its discovery to clinical applications. International Immunology 22 (5): 347–352. https://doi.org/10.1093/intimm/dxq030.CrossRefPubMed

73.

Jatakanon, A., C. Uasuf, W. Maziak, S. Lim, K.F. Chung, and P.J. Barnes. 1999. Neutrophilic inflammation in severe persistent asthma. American Journal of Respiratory and Critical Care Medicine 160 (5 Pt 1): 1532–1539. https://doi.org/10.1164/ajrccm.160.5.9806170.CrossRefPubMed

74.

Liu, L., Q. Li, P. Han, X. Li, H. Zeng, Y. Zhu, and Q. Wei. 2009. Evaluation of interleukin-8 in expressed prostatic secretion as a reliable biomarker of inflammation in benign prostatic hyperplasia. Urology 74 (2): 340–344. https://doi.org/10.1016/j.urology.2009.02.064.CrossRefPubMed

75.

Hill, S.L., J.L. Mitchell, D. Burnett, and R.A. Stockley. 1998. IgG subclasses in the serum and sputum from patients with bronchiectasis. Thorax 53 (6): 463–468. https://doi.org/10.1136/thx.53.6.463.CrossRefPubMedPubMedCentral

Titel: The Emerging Roles of T Helper Cell Subsets and Cytokines in Severe Neutrophilic Asthma
verfasst von: Qi Chen
Siji Nian
Yingchun Ye
Dan Liu
Hong Yu
Hong Xiong
Bi Pan
Lu Xiao
Chunrong Fan
Qing Yuan
Publikationsdatum: 26.11.2021
Verlag: Springer US
Erschienen in: Inflammation / Ausgabe 3/2022
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-021-01598-6

Enhanced Responsive Formation of Extracellular Traps in Macrophages Previously Exposed to Porphyromonas gingivalis

Original Article

Lipopolysaccharide Accelerates Neuropilin-1 Protein Degradation by Activating the Large GTPase Dynamin-1 in Macrophages

Original Article

Expressions of Interleukin-27 in Oral Lichen Planus, Oral Leukoplakia, and Oral Squamous Cell Carcinoma

Original Article

Autonomic Disbalance During Systemic Inflammation is Associated with Oxidative Stress Changes in Sepsis Survivor Rats

Original Article

MiR-15p-5p Mediates the Coordination of ICAM-1 and FAK to Promote Endothelial Cell Proliferation and Migration

Original Article

Sigma-1 Receptor Alleviates Airway Inflammation and Airway Remodeling Through AMPK/CXCR4 Signal Pathway

Original Article

Kompaktes Leitlinien-Wissen Innere Medizin (Link öffnet in neuem Fenster)

Mit medbee Pocketcards schnell und sicher entscheiden.
Leitlinien-Wissen kostenlos und immer griffbereit auf ihrem Desktop, Handy oder Tablet.

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Antibiotika bei Bakteriämie – 7 versus 14 Tage

21.01.2025
Sepsis
Nachrichten

Eine Bakteriämie lässt sich mit einer einwöchigen Antibiotikatherapie zumeist gut in den Griff bekommen: Die Sterberate ist nicht höher als unter zweiwöchiger Behandlung, zeigt eine Vergleichsstudie mit hospitalisierten Erkrankten. Allerdings muss die Therapie bei fast jedem Vierten verlängert werden.

"Die Erektionsstörung ist keine isolierte Erkrankung"

21.01.2025
Erektile Dysfunktion
Podcast

Werden Erektionsstörungen gut behandelt (und das ist möglich), steigt die Lebensqualität enorm. Tipps für eine gute Kommunikation mit den Patienten gibt Androloge Dr. med. Jann-Frederik Cremers in dieser Folge. Welche Fragen sollten gestellt und an welche Ursachen gedacht werden? Und was ist zu tun, wenn PDE-5-Hemmer und Lebensstilveränderungen nicht ausreichend wirken?

Lp(a) zur Risikoeinschätzung bei Thoraxschmerzen

20.01.2025
Koronare Herzerkrankung
Nachrichten

Der Lp(a)-Wert kann dazu beitragen, bei stabilen Patienten mit neu aufgetretenen Thoraxschmerzen und ohne KHK-Diagnose die Wahrscheinlichkeit für das Vorliegen von Koronarstenosen abzuschätzen.

Finerenon bei eGFR-Verlust nicht gleich absetzen!

20.01.2025
Chronische Herzinsuffizienz
Nachrichten

Der Mineralokortikoid-Rezeptor-Antagonist Finerenon verbessert die Prognose bei Herzinsuffizienz mit leicht reduzierter oder erhaltener Ejektionsfraktion. Ein Rückgang der eGFR zu Beginn der Therapie scheint diese Wirkung nicht wesentlich zu mindern.

EKG Essentials: EKG befunden mit System (Link öffnet in neuem Fenster)

In diesem CME-Kurs können Sie Ihr Wissen zur EKG-Befundung anhand von zwölf Video-Tutorials auffrischen und 10 CME-Punkte sammeln.
Praxisnah, relevant und mit vielen Tipps & Tricks vom Profi.

Jetzt 10 CME-Punkte sammeln

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

The Emerging Roles of T Helper Cell Subsets and Cytokines in Severe Neutrophilic Asthma

Abstract—

Weitere Artikel der Ausgabe 3/2022

Enhanced Responsive Formation of Extracellular Traps in Macrophages Previously Exposed to Porphyromonas gingivalis

Lipopolysaccharide Accelerates Neuropilin-1 Protein Degradation by Activating the Large GTPase Dynamin-1 in Macrophages

Expressions of Interleukin-27 in Oral Lichen Planus, Oral Leukoplakia, and Oral Squamous Cell Carcinoma

Autonomic Disbalance During Systemic Inflammation is Associated with Oxidative Stress Changes in Sepsis Survivor Rats

MiR-15p-5p Mediates the Coordination of ICAM-1 and FAK to Promote Endothelial Cell Proliferation and Migration

Sigma-1 Receptor Alleviates Airway Inflammation and Airway Remodeling Through AMPK/CXCR4 Signal Pathway

Kompaktes Leitlinien-Wissen Innere Medizin (Link öffnet in neuem Fenster)

Neu im Fachgebiet Innere Medizin

Antibiotika bei Bakteriämie – 7 versus 14 Tage

"Die Erektionsstörung ist keine isolierte Erkrankung"

Lp(a) zur Risikoeinschätzung bei Thoraxschmerzen

Finerenon bei eGFR-Verlust nicht gleich absetzen!

EKG Essentials: EKG befunden mit System (Link öffnet in neuem Fenster)

Update Innere Medizin

Springer Medizin

Abstract—

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten