T helper 1 cells stimulated with ovalbumin and IL-18 induce airway hyperresponsiveness and lung fibrosis by IFN-γ and IL-13 production

Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 10/2007; 104(37):14765-70. DOI: 10.1073/pnas.0706378104
Source: PubMed

ABSTRACT We previously reported that ovalbumin (OVA) and IL-18 nasally administered act on memory type T helper (Th)1 cells to induce airway hyperresponsiveness (AHR) and inflammation, which is characterized by peribronchial infiltration with neutrophils and eosinophils. Here, we report this administration also induces lung fibrosis in an IL-13-dependent manner. Th1 cells secrete several cytokines, including IFN-gamma and bronchogenic cytokine IL-13, when stimulated with antigen (Ag) and IL-18. However, IL-13 blockade failed to attenuate AHR, although this treatment inhibited eosinophilic infiltration. To understand the mechanism by which Th1 cells induce AHR after Ag plus IL-18 challenge, we established "passive" and "active" Th1 mice by transferring OVA-specific Th1 cells into naïve BALB/c mice or by immunizing naïve BALB/c mice with OVA/complete Freund's adjuvant, respectively. Administration of Ag and IL-18 induced both types of Th1 mice to develop AHR, airway inflammation, and lung fibrosis. Furthermore, this treatment induced deposition of periostin, a novel component of lung fibrosis. Neutralization of IL-13 or IFN-gamma during Ag plus IL-18 challenges inhibited the combination of eosinophilic infiltration, lung fibrosis, and periostin deposition or the combination of neutrophilic infiltration and AHR, respectively. We also found that coadministration of OVA and LPS into Th1 mice induced AHR and airway inflammation via endogenous IL-18. Thus, IL-18 becomes a key target molecule for the development of a therapeutic regimen for the treatment of Th1-cell-induced bronchial asthma.

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Available from: Toshio Tanaka, Aug 20, 2015
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    • "CBRM1/5 α M I domain High-activity Oxvig et al. (1999), Byron et al. (2009) EGF, epidermal growth factor; PSI, plexin-semaphorin-integrin. type 2 (Th2) cytokines in bronchial epithelial cells and lung fibroblasts and is deposited in patients with asthma and atopic dermatitis, as well as in animal models of asthma and allergic skin inflammation (Yuyama et al., 2002; Takayama et al., 2006; Hayashi et al., 2007; Woodruff et al., 2007; Masuoka et al., 2012). Mice lacking periostin respond to lung antigen challenge with significantly decreased number of eosinophils in the lung and have reduced allergic skin inflammation (Blanchard et al., 2008; Bentley et al., 2012; Masuoka et al., 2012), thus implicating periostin as a ligand in eosinophil recruitment and retention in allergy and asthma. "
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    Frontiers in Pharmacology 04/2013; 4:33. DOI:10.3389/fphar.2013.00033 · 3.80 Impact Factor
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    • "Additionally, Th17 cells can even stop producing IL-17 and become selective IFNγ producers resulting in a complete subset switch (O'Shea and Paul 2010). Although Th1 cells do not become IL-17 producers, under particular circumstances they can make IL-13 (Hayashi et al. 2007). Th17 cells produce IL-22, but cells that make IL-22 and not IL-17 ( " Th22 cells " ) have recently been identified as well (Duhen et al. 2009; Trifari et al. 2009). "
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    • "Our study provides evidence that the increase in serum levels of the Th2-type cytokine IL-5 due to the induction of experimental asthma in C57BL/6 mice, which preferentially mount a Th1-type inflammatory response [23], seems to depend partly on the presence of endogenous IL-18. Upon stimulation with antigen plus IL-18 Th1 cells at least in vitro might develop into ultra-inflaming T cells [7] [24] or super Th1 cells [25], able to secrete Th1-type and a limited set of Th2-type cytokines and to induce asthma or atopic dermatitis. Thus, in the C57BL/6 model of OVA-induced experimental asthma, naı¨ve Th cells probably develop mostly into Th2 cells inducing asthmatic symptoms, while the development of ultra-inflaming T cells, which would depend on endogenous IL-18, is of minor relevance for this process. "
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