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A promoter nucleotide variant of the dendritic cell-specific DCNP1 associates with serum IgE levels specific for dust mite allergens among the Korean asthmatics

Genes & Immunity volume 8, pages 369–378 (2007)Cite this article

Abstract

Dendritic cells (DCs), the most abundant antigen-presenting cells in the lung, have been drawing attention for their roles in specific allergic responses to aeroallergens with support of Th lymphocytes, and in persistent inflammatory changes in allergic asthma. To identify genetic factors that may be involved in the asthma susceptibility and development of the disease phenotypes, we examined association of DC-specific DCNP1 polymorphisms with the disease risk. The case–control study revealed association of the nucleotide variants with serum immunoglobulin E (IgE) levels specific for Dermatophagoides farinae (Der f 1) and Dermatophagoides pteronyssinus (Der p 1), major aeroallergens of dust mites, among subjects with asthma. In particular, the T-allele-carrying genotype frequencies for one of the variants (c.−1289C>T) located in the promoter region were found increased in the asthmatic group with low levels of the mite-specific IgE (odds ratio (OR)=0.63 (0.48–0.83) for Der p 1). Results from functional analyses indicated that the promoter variant would affect the gene expression by modulating DNA–protein interaction. We propose that the genetic polymorphism of DCNP1 may influence production of specific IgE by altering DC functions in the mite allergen presenting and/or processing. The functional relevance of the genetic variation would provide an important insight into the genetic basis of allergic response to the mite antigens.

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References

  1. Sengler C, Lau S, Wahn U, Nickel R . Interactions between genes and environmental factors in asthma and atopy: new developments. Respir Res 2002; 3: 7.

    Article  Google Scholar 

  2. Kabesch M . Gene by environment interactions and the development of asthma and allergy. Toxicol Lett 2006; 162: 43–48.

    Article  CAS  Google Scholar 

  3. Larche M, Robinson DS, Kay AB . The role of T lymphocytes in the pathogenesis of asthma. J Allergy Clin Immunol 2003; 111: 450–463; quiz 464.

    Article  CAS  Google Scholar 

  4. Herrick CA, Bottomly K . To respond or not to respond: T cells in allergic asthma. Nat Rev Immunol 2003; 3: 405–412.

    Article  CAS  Google Scholar 

  5. van Rijt LS, Lambrecht BN . Role of dendritic cells and Th2 lymphocytes in asthma: lessons from eosinophilic airway inflammation in the mouse. Microsc Res Tech 2001; 53: 256–272.

    Article  CAS  Google Scholar 

  6. Maldonado-Lopez R, Maliszewski C, Urbain J, Moser M . Cytokines regulate the capacity of CD8alpha(+) and CD8alpha(-) dendritic cells to prime Th1/Th2 cells in vivo. J Immunol 2001; 167: 4345–4350.

    Article  CAS  Google Scholar 

  7. Pulendran B, Smith JL, Caspary G, Brasel K, Pettit D, Maraskovsky E et al. Distinct dendritic cell subsets differentially regulate the class of immune response in vivo. Proc Natl Acad Sci USA 1999; 96: 1036–1041.

    Article  CAS  Google Scholar 

  8. Vieira PL, de Jong EC, Wierenga EA, Kapsenberg ML, Kalinski P . Development of Th1-inducing capacity in myeloid dendritic cells requires environmental instruction. J Immunol 2000; 164: 4507–4512.

    Article  CAS  Google Scholar 

  9. Hammad H, Lambrecht BN . Recent progress in the biology of airway dendritic cells and implications for understanding the regulation of asthmatic inflammation. J Allergy Clin Immunol 2006; 118: 331–336.

    Article  CAS  Google Scholar 

  10. Masuda M, Senju S, Fujii Si S, Terasaki Y, Takeya M, Hashimoto Si S et al. Identification and immunocytochemical analysis of DCNP1, a dendritic cell-associated nuclear protein. Biochem Biophys Res Commun 2002; 290: 1022–1029.

    Article  CAS  Google Scholar 

  11. Hizawa N, Freidhoff LR, Ehrlich E, Chiu YF, Duffy DL, Schou C et al. Genetic influences of chromosomes 5q31-q33 and 11q13 on specific IgE responsiveness to common inhaled allergens among African American families. Collaborative Study on the Genetics of Asthma (CSGA). J Allergy Clin Immunol 1998; 102: 449–453.

    Article  CAS  Google Scholar 

  12. Rioux JD, Daly MJ, Silverberg MS, Lindblad K, Steinhart H, Cohen Z et al. Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease. Nat Genet 2001; 29: 223–228.

    Article  CAS  Google Scholar 

  13. Kabesch M, Carr D, Weiland SK, von Mutius E . Association between polymorphisms in serine protease inhibitor, kazal type 5 and asthma phenotypes in a large German population sample. Clin Exp Allergy 2004; 34: 340–345.

    Article  CAS  Google Scholar 

  14. Ober C, Moffatt MF . Contributing factors to the pathobiology. The genetics of asthma. Clin Chest Med 2000; 21: 245–261.

    Article  CAS  Google Scholar 

  15. Hoffjan S, Ober C . Present status on the genetic studies of asthma. Curr Opin Immunol 2002; 14: 709–717.

    Article  CAS  Google Scholar 

  16. Blumenthal MN . The role of genetics in the development of asthma and atopy. Curr Opin Allergy Clin Immunol 2005; 5: 141–145.

    Article  CAS  Google Scholar 

  17. Mizumoto N, Hui F, Edelbaum D, Weil MR, Wren JD, Shalhevet D et al. Differential activation profiles of multiple transcription factors during dendritic cell maturation. J Invest Dermatol 2005; 124: 718–724.

    Article  CAS  Google Scholar 

  18. Kabesch M, Schedel M, Carr D, Woitsch B, Fritzsch C, Weiland SK et al. IL-4/IL-13 pathway genetics strongly influence serum IgE levels and childhood asthma. J Allergy Clin Immunol 2006; 117: 269–274.

    Article  CAS  Google Scholar 

  19. Looney RJ, Pudiak D, Rosenfeld SI . Cytokine production by mite-specific T cells from donors with mild atopic disease. J Allergy Clin Immunol 1994; 93: 476–483.

    Article  CAS  Google Scholar 

  20. Koh YY, Jeong JH, Kim CK, Kim YK, Jee YK, Cho SH et al. Atopic status and level of bronchial responsiveness in parents of children with acute bronchiolitis. J Asthma 2000; 37: 709–717.

    Article  CAS  Google Scholar 

  21. Hammad H, Charbonnier AS, Duez C, Jacquet A, Stewart GA, Tonnel AB et al. Th2 polarization by Der p 1 – pulsed monocyte-derived dendritic cells is due to the allergic status of the donors. Blood 2001; 98: 1135–1141.

    Article  CAS  Google Scholar 

  22. Keane-Myers AM, Gause WC, Finkelman FD, Xhou XD, Wills-Karp M . Development of murine allergic asthma is dependent upon B7-2 costimulation. J Immunol 1998; 160: 1036–1043.

    CAS  PubMed  Google Scholar 

  23. Tsuyuki S, Tsuyuki J, Einsle K, Kopf M, Coyle AJ . Costimulation through B7-2 (CD86) is required for the induction of a lung mucosal T helper cell 2 (TH2) immune response and altered airway responsiveness. J Exp Med 1997; 185: 1671–1679.

    Article  CAS  Google Scholar 

  24. MacPhee IA, Turner DR, Yagita H, Oliveira DB . CD80(B7.1) and CD86(B7.2) do not have distinct roles in setting the Th1/Th2 balance in autoimmunity in rats. Scand J Immunol 2001; 54: 486–494.

    Article  CAS  Google Scholar 

  25. Harris NL, Prout M, Peach RJ, Fazekas de St Groth B, Ronchese F . CD80 costimulation is required for Th2 cell cytokine production but not for antigen-specific accumulation and migration into the lung. J Immunol 2001; 166: 4908–4914.

    Article  CAS  Google Scholar 

  26. Pichavant M, Charbonnier AS, Taront S, Brichet A, Wallaert B, Pestel J et al. Asthmatic bronchial epithelium activated by the proteolytic allergen Der p 1 increases selective dendritic cell recruitment. J Allergy Clin Immunol 2005; 115: 771–778.

    Article  CAS  Google Scholar 

  27. Tunon-De-Lara JM, Redington AE, Bradding P, Church MK, Hartley JA, Semper AE et al. Dendritic cells in normal and asthmatic airways: expression of the alpha subunit of the high affinity immunoglobulin E receptor (Fc epsilon RI-alpha). Clin Exp Allergy 1996; 26: 648–655.

    Article  CAS  Google Scholar 

  28. Moller GM, Overbeek SE, Van Helden-Meeuwsen CG, Van Haarst JM, Prens EP, Mulder PG et al. Increased numbers of dendritic cells in the bronchial mucosa of atopic asthmatic patients: downregulation by inhaled corticosteroids. Clin Exp Allergy 1996; 26: 517–524.

    Article  CAS  Google Scholar 

  29. Udey MC . Gone fishin' in 2005 – insights into the inner workings of dendritic cells. J Invest Dermatol 2005; 124: vi–vii.

    Article  CAS  Google Scholar 

  30. Huh JC, Strickland DH, Jahnsen FL, Turner DJ, Thomas JA, Napoli S et al. Bidirectional interactions between antigen-bearing respiratory tract dendritic cells (DCs) and T cells precede the late phase reaction in experimental asthma: DC activation occurs in the airway mucosa but not in the lung parenchyma. J Exp Med 2003; 198: 19–30.

    Article  CAS  Google Scholar 

  31. Chai H, Farr RS, Froehlich LA, Mathison DA, McLean JA, Rosenthal RR et al. Standardization of bronchial inhalation challenge procedures. J Allergy Clin Immunol 1975; 56: 323–327.

    Article  CAS  Google Scholar 

  32. Stephens M, Smith NJ, Donnelly P . A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 2001; 68: 978–989.

    Article  CAS  Google Scholar 

  33. Xu S, Ariizumi K, Caceres-Dittmar G, Edelbaum D, Hashimoto K, Bergstresser PR et al. Successive generation of antigen-presenting, dendritic cell lines from murine epidermis. J Immunol 1995; 154: 2697–2705.

    CAS  PubMed  Google Scholar 

  34. Benjamini Y, Hochberg Y . Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Royal Stat Soc B 1995; 57: 289–300.

    Google Scholar 

  35. Hochberg Y . A sharper Bonferroni procedure for multiple tests of significance. Biometrika 1988; 75: 800–802.

    Article  Google Scholar 

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Acknowledgements

We are grateful to Dr Akira Takashima from University of Texas Southwestern Medical Center for generously donating us XS106 and NS47 cells for this study. We also thank Dr Yasuharu Nishimura's group from Kumamoto University for advices concerning DC line selection for transfection. We appreciate Hye Ree Han and Min Jin Go's helpful comments on the association analyses. This work was supported by the National Institute of Health (National Budget Code 348-6111-221), Korea Health 21 R&D Project (00-PJ3-PG6-GN07-001) and the Ministry of Health & Welfare, Republic of Korea (01-PJ3-PG6-01GN04-003).

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Author notes

  1. Y Kim, C-S Park and H D Shin: These authors equally contributed to this work.

Authors and Affiliations

  1. The Center for Genome Science, National Institute of Health, Seoul, Korea

    Y Kim, J-W Choi, E J Lee, S G Park, J-Y Lee, J-K Lee, B G Han, B Oh & K Kimm

  2. Genome Research Center for Allergy and Respiratory Diseases, Soonchunhyang University Bucheon Hospital and Seoul Hospital, Seoul, Korea

    C-S Park, A S Jang, S W Park & Y M Lee

  3. Department of Genetic Epidemiology, SNP Genetics Inc., Seoul, Korea

    H D Shin, H S Cheong, B L Park & Y H Choi

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  1. Y Kim
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Correspondence to K Kimm.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Kim, Y., Park, CS., Shin, H. et al. A promoter nucleotide variant of the dendritic cell-specific DCNP1 associates with serum IgE levels specific for dust mite allergens among the Korean asthmatics. Genes Immun 8, 369–378 (2007). https://doi.org/10.1038/sj.gene.6364394

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