Heat shock protein X purified from Mycobacterium tuberculosis enhances the efficacy of dendritic cells-based immunotherapy for the treatment of allergic asthma
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Dendritic cells play an important role in determining whethernaïve T cells mature into either Th1 or Th2 cells. We determinedwhether heat-shock protein X (HspX) purified fromMycobacterium tuberculosis regulates the Th1/Th2 immuneresponse in an ovalbumin (OVA)-induced murine model ofasthma. HspX increased interferon-gamma, IL-17A, -12 andtransforming growth factor (TGF)- production and T-bet geneexpression but reduced IL-13 production and GATA-3 geneexpression. HspX also inhibited asthmatic reactions as demonstratedby an increase in the number of eosinophils in bronchoalveolarlavage fluid, inflammatory cell infiltration in lungtissues, airway luminal narrowing, and airway hyper-responsiveness. Furthermore, HspX enhanced OVA-induced decreaseof regulatory T cells in the mediastinal lymph nodes. Thisstudy provides evidence that HspX plays critical roles in theamelioration of asthmatic inflammation in mice. These findingsprovide new insights into the immunotherapeutic role ofHspX with respect to its effects on a murine model of asthma.
Abstract
Dendritic cells play an important role in determining whethernaïve T cells mature into either Th1 or Th2 cells. We determinedwhether heat-shock protein X (HspX) purified fromMycobacterium tuberculosis regulates the Th1/Th2 immuneresponse in an ovalbumin (OVA)-induced murine model ofasthma. HspX increased interferon-gamma, IL-17A, -12 andtransforming growth factor (TGF)- production and T-bet geneexpression but reduced IL-13 production and GATA-3 geneexpression. HspX also inhibited asthmatic reactions as demonstratedby an increase in the number of eosinophils in bronchoalveolarlavage fluid, inflammatory cell infiltration in lungtissues, airway luminal narrowing, and airway hyper-responsiveness. Furthermore, HspX enhanced OVA-induced decreaseof regulatory T cells in the mediastinal lymph nodes. Thisstudy provides evidence that HspX plays critical roles in theamelioration of asthmatic inflammation in mice. These findingsprovide new insights into the immunotherapeutic role ofHspX with respect to its effects on a murine model of asthma.
참고문헌 (31)
- Franchini M, "The role of neutrophil chemotactic cytokines in the pathogenesis of equine chronic obstructive pulmonary disease(COPD)", Vet Immunol Immunopathol, 66, pp.53~65 (1998)
- Yawn BP, "Factors accounting for asthma variability:achieving optimal symptom control for individual patients", Prim Care Respir J, 17, pp.138~147 (2008)
- Spicuzza L, "Research applications and implications of adenosine in diseased airways", Trends Pharmacol Sci, 24, pp.409~413 (2003)
- Mapp CE, "Pathogenesis of late asthmatic reactions induced by exposure to isocyanates", Bull Eur Physiopathol Respir, 23, pp.583~586 (1987)
- Bousquet J, "Eosinophilic inflammation in asthma", N Engl J Med, 323, pp.1033~1039 (1990)
- Kay AB, "Asthma and inflammation", J Allergy Clin Immunol, 87, pp.893~910 (1991)
- Geluk A, "T-cell recognition of the HspX protein of Mycobacterium tuberculosis correlates with latent M. tuberculosis infection but not with M. bovis BCG vaccination", Infect Immun, 75, pp.2914~2921 (2007)
- Lagranderie M, "Mycobacterium bovis BCG killed by extended freeze-drying reduces airway hyperresponsiveness in 2 animal models", J Allergy Clin Immunol, 121, pp.471~478 (2008)
- Byun EH, "Mycobacterium tuberculosis Rv0577, a novel TLR2 agonist, induces maturation of dendritic cells and drives Th1 immune response", FASEB J, 26, pp.2695~2711 (2012)
- Furuta K, "Encounter with antigen-specific primed CD4 T cells promotes MHC class II degradation in dendritic cells", Proc Natl Acad Sci U S A, 109, pp.19380~19385 (2012)
- Wu Z, "Generation and characterization of chicken bone marrow-derived dendritic cells", Immunology, 129, pp.133~145 (2010)
- Zhang X, "Unequal death in T helper cell (Th)1 and Th2 effectors: Th1, but not Th2, effectors undergo rapid Fas", FasL-mediated apoptosis, 1997, pp.185, 1837~1849
- Ozdemir C, "T regulatory cells and their counterparts: masters of immune regulation", Clin Exp Allergy, 39, pp.626~639 (2009)
- Hamza E, "In vitro induction of functional allergen-specific CD4+ CD25high Treg cells in horses affected with insect bite hypersensitivity", Clin Exp Allergy, 43, pp.889~901 (2013)
- Wing JB, "Foxp3(+)T(reg)cells in humoral immunity", Int Immunol, 26, pp.61~69 (2014)
- Tanaka H, "Role of interleukin-5 and eosinophils in allergen-induced airway remodeling in mice", Am J Respir Cell Mol Biol, 31, pp.62~68 (2004)
- Corrigan CJ, "T cells and eosinophils in the pathogenesis of asthma", Immunol Today, 13, pp.501~507 (1992)
- Iwamoto I, "Interferon gamma regulates antigen-induced eosinophil recruitment into the mouse airways by inhibiting the infiltration of CD4+ T cells", J Exp Med, 177, pp.573~576 (1993)
- Sur S, "Immunomodulatory effects of IL-12 on allergic lung inflammation depend on timing of doses", J Immunol, 157, pp.4173~4180 (1996)
- Ho IC, "Human GATA-3:a lineage-restricted transcription factor that regulates the expression of the T cell receptor alpha gene", EMBO J, 10, pp.1187~1192 (1991)
- Zhou M, "The function role of GATA-3 in Th1 and Th2 differentiation", Immunol Res, 28, pp.25~37 (2003)
- Szabo SJ, "A novel transcription factor, T-bet, directs Th1 lineage commitment", Cell, 100, pp.655~669 (2000)
- Miller SA, "Molecular mechanisms by which T-bet regulates T-helper cell commitment", Immunol Rev, 238, pp.233~246 (2010)
- Szabo SJ, "Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells", Science, 295, pp.338~342 (2002)
- Zheng J, "Generation of human Th1-like regulatory CD4+ T cells by an intrinsic IFN-gamma-and T-bet-dependent pathway", Eur J Immunol, 41, pp.128~139 (2011)
- Mullen AC, "Role of T-bet in commitment of TH1 cells before IL-12-dependent selection", Science, 292, pp.1907~1910 (2001)
- Bian T, "Treatment of allergic airway inflammation and hyperresponsiveness by imiquimod modulating transcription factors T-bet and GATA-3", Chin Med J (Engl), 119, pp.640~648 (2006)
- Afkarian M, "T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells", Nat Immunol, 3, pp.549~557 (2002)
- Gregoire JM, "T-cell expression of the human GATA-3 gene is regulated by a non-lineage-specific silencer", J Biol Chem, 274, pp.6567~6578 (1999)
- Jung ID, "Enhanced efficacy of therapeutic cancer vaccines produced by co-treatment with Mycobacterium tuberculosis heparin-binding hemagglutinin, a novel TLR4 agonist", Cancer Res, 71, pp.2858~2870 (2011)
- 정인덕, "RG-II from Panax ginseng C.A. Meyer suppresses asthmatic reaction", BMB Reports, 45(2), pp.79~84 (2012), 생화학분자생물학회