Abstract Objective To determine the proportion of Tc17 cells in the lungs of mice with neutrophilic(NEU) asthma, and to investigate the role of Tc17 cells in the pathogenesis of NEU asthma.Methods Thirty-two C57/B6 mice of clean grade were randomly divided into two groups:NEU asthma and control.The mice in the NEU asthma group were sensitized by airway instillation of ovalbumin(OVA) and lipopolysaccharide(LPS), and challenged with an aerosol of OVA, while those in the control group were sensitized and challenged with normal saline.At 24 hours after the final challenge, bronchoalveolar lavage fluid(BALF) was collected, and the total number and differential counts of nucleated cells and percentage of each type were determined.The lung tissues were separated and hematoxylin-eosin staining was performed to observe the pathological changes of lungs;flow cytometry was applied to determine the percentages of Tc17 and Th17 cells in the lung tissues.Enzyme-linked immunosorbent assay was applied to determine the levels of interleukin-6(IL-6), transforming growth factor β(TGF-β), and interleukin-17(IL-17) in BALF.Results The NEU asthma group had a significantly higher total number of nucleated cells, a significantly higher percentage of eosinophils, and a significantly higher percentage of neutrophils in BALF than the control group(PPPPConclusions The expression of Tc17 cells in the lung tissues increases in mice with NEU asthma, and the increased number of Tc17 cells may be involved in the pathogenesis of NEU asthma.Tc17 cells may play an important role in NEU asthma through IL-17.
McGrath KW, Icitovic N, Boushey HA,et al. Asthma Clinical Research Network of the National Heart L, Blood I:A large subgroup of mild-to-moderate asthma is persistently noneosinophilic[J]. Am J Respir Crit Care Med, 2012, 185(6):612-619.
Uddin M, Nong G, Ward JS, et al. Prosurvival activity for airway neutrophils in severe asthma[J]. Thorax, 2010, 65(8):684-689.
[5]
Newcomb DC, Peebles RS Jr. Th17-mediated inflammation in asthma[J]. Curr Opin Immunol, 2013, 25(6):755-760.
[6]
Ano S, Morishima Y, Ishii Y, et al. Transcription factors GATA-3 and RORgammat are important for determining the phenotype of allergic airway inflammation in a murine model of asthma[J]. J Immunol, 2013, 190(3):1056-1065.
[7]
Wilson RH, Whitehead GS, Nakano H, et al. Allergic sensitization through the airway primes Th17-dependent neutrophilia and airway hyperresponsiveness[J]. Am J Respir Crit Care Med, 2009, 180(8):720-730.
[8]
Ortega C, Fernandez AS, Carrillo JM, et al. IL-17-producing CD8+ T lymphocytes from psoriasis skin plaques are cytotoxic effector cells that secrete Th17-related cytokines[J]. J Leukoc Biol, 2009, 86(2):435-443.
[9]
Li K, Wang Z, Cao Y, et al. The study of the ratio and distribution of Th17 cells and Tc17 cells in asthmatic patients and the mouse model[J]. Asian Pac J Allergy Immunol, 2013, 31(2):125-131.
Jatakanon A, Uasuf C, Maziak W, et al. Neutrophilic inflammation in severe persistent asthma[J]. Am J Respir Crit Care Med, 1999, 160(5 Pt 1):1532-1539.
[12]
Anderson GP. Endotyping asthma:new insights into key pathogenic mechanisms in a complex, heterogeneous disease[J]. Lancet, 2008, 372(9643):1107-1119.
[13]
Henness S, van Thoor E, Ge Q, et al. IL-17A acts via p38 MAPK to increase stability of TNF-alpha-induced IL-8 mRNA in human ASM[J]. Am J Physiol Lung Cell Mol Physiol, 2006, 290(6):L1283-1290.
[14]
Tajima M, Wakita D, Noguchi D, et al. IL-6-dependent spontaneous proliferation is required for the induction of colitogenic IL-17-producing CD8+ T cells[J]. J Exp Med, 2008, 205(5):1019-1027.
Huber M, Heink S, Pagenstecher A, et al. IL-17A secretion by CD8+ T cells supports Th17-mediated autoimmune encephalomyelitis[J]. J Clin Invest, 2013, 123(1):247-260.