Identification of Polymorphisms in Thymic Stromal Lymphopoietin (TSLP) Gene and Their Association with Allergic Rhinitis

Zhang, Mei-Hua;Kim, Yong-Shin;Jin, Eun-Heui;Kim, Ki-Mo;Lee, Jae-Hoon;Li, Chun-Shi;Zhang, Qinggao;Yun, Ki-Jung;Chae, Soo-Cheon;Chung, Hun-Taeg

  • Published : 20081000

Abstract

Dendritic cell (DC) activator, thymic stromal lymphopoietin (TSLP) induces DCs to produce Th2-attracting chemokines, causing differentiation of CD4+ and CD8+ T cells into effector cells. The differentiated cells are characterized by a typical pro-allergic phenotype. In this study, we identified four single nucleotide polymorphisms (SNPs) and one variation site (g.-305delT ) from the results of scanned human TSLP gene. The SNPs are as following: g.-1914A >G and g.-847C > T in promoter, g.-82C > T in 5' UTR and g.1117C > T in intron 2. We also evaluated the association of genotype and allele frequencies of these SNPs between non-allergic rhinitis controls and allergic rhinitis patients. We further investigated possible correlations between each genotype with serum total IgE levels and peripheral blood eosinophil counts in allergic rhinitis patients. The frequencies of haplotype constructed by these SNPs between these two groups were also compared. Our results demonstrate the two SNPs (g.-1914A >G and g.-847C > T ) were associated with susceptibility of allergic rhinitis (P = 0.006 and P = 0.015 respectively), however, serum total IgE levels were not significantly related with the SNPs.

Keywords

References

  1. Chae SC, Park YR, Li SC, Lee JH, Yang YS, Zhang Q, Kim KS and Chung HT (2006) Analysis of the variations in IL-28RA gene and their association with allergic rhinitis. Exp. Mol. Med. 38: 302-309 https://doi.org/10.1038/emm.2006.36
  2. Chae S C, P ark YR, O h G J, L ee JH a nd C hung H T (2005) The suggestive association of eotaxin-2 and eotaxin-3 gene polymorphisms in Korean population with allergic rhinitis. Immunogenetics. 56: 760-764 https://doi.org/10.1007/s00251-004-0746-2
  3. Chae SC, Song JH, Pounsambath P, Yuan HY, Lee JH, Kim JJ, Lee YC and Chung HT (2004) Molecular variations in Th1-specific cell surface gene Tim-3. Exp. Mol. Med. 30: 274-278
  4. Cheng L, Enomoto T, Hirota T, Shimizu M, Takahashi N, Akahoshi M, Matsuda A, Dake Y, Doi S, Enomoto K, Yamasaki A, Fukuda S, Mao XQ, Hopkin JM, Tamari M and Shirakawa T (2004) Polymorphisms in ADAM33 are associated with allergic rhinitis due to Japanese ceder pollen. Clin. Exp. Allergy 34: 1192-1201 https://doi.org/10.1111/j.1365-2222.2004.02008.x
  5. Daser A, Meissner N, Herz U and Renz H (1995) Role and modulation of T-cell cytokines in allergy. Curr. Opin. Immunol. 7: 762-770 https://doi.org/10.1016/0952-7915(95)80045-X
  6. Ho IC and Glimcher LH (2002) Transcription: Tantalizing Times for T Cells. Cell 109: S109-120 https://doi.org/10.1016/S0092-8674(02)00705-5
  7. Ito T, Wang YH, Duramad O, Hori T, Delespesse GJ, Watanabe N, Qin FXF, Yao Z, Cao W and Liu YJ (2005) TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand. J. Exp. Med. 202: 1213-1223 https://doi.org/10.1084/jem.20051135
  8. Kay AB (2001) Allergy and allergic diseases. Second of two parts. N. Engl. J. Med. 344: 109-113 https://doi.org/10.1056/NEJM200101113440206
  9. Leonard WJ (2002) TSLP: finally in the limelight. Nature lmmunol. 3: 605-607 https://doi.org/10.1038/ni0702-605
  10. Lichtman AH and Abbas AK (1997) T-cell subsets: recruiting the right kind of help. Curr. Biol. 7: R242-244 https://doi.org/10.1016/S0960-9822(06)00111-4
  11. Li CS, Chae SC, Lee JH, Zhang Q and Chung HT (2006) Identification of single nucleotide polymorphisms in FOXJ1 and their association with allergic rhinitis. J. Hum. Genet. 51: 292-297 https://doi.org/10.1007/s10038-006-0359-8
  12. Liu YJ (2006) Thymic stromal lymphopoietin: mast switch for allergic inflammation. J. Exp. Med. 203: 269-273 https://doi.org/10.1084/jem.20051745
  13. O'Garra A (1998) Cytokines induce the development of functional heterogeneous T helper cell subsets. Immunity. 8: 275-283 https://doi.org/10.1016/S1074-7613(00)80533-6
  14. Passali D, Lauriello M, Mezzedimi C, Passali GC and Bellussi L (2001) Natural history of allergic rhinitis a review. Clin. Applied. Immunol. Rev. 1: 207-216 https://doi.org/10.1016/S1529-1049(01)00016-2
  15. Reche PA, Soumelis V, Gorman DM, Clifford T, Liu M, Trav is M, Zurawski SM, Johnston J, Liu YJ, Spits H, de Waal Malefyt R, Kastelein RA and Bazan JF (2001) Human thymic stromal lymphopoietin preferentially stimulates myeloid cell. J. Immunol. 167: 336-343 https://doi.org/10.4049/jimmunol.167.1.336
  16. Renauld JC (2001) New insights into the role of cytokines in asthma. J. Clin. Pathol. 54: 577-589 https://doi.org/10.1136/jcp.54.8.577
  17. Soumelis V, Reche PA, Kanzler H, Yuan W, Edward G, Homey B, Gilliet M, Ho S, Antonenko S, Lauerma A, Smith K, Gorman D, Zurawski S, Abrams J, Menon S, McClanahan T, de Waal-Malefyt Rd R, Bazan F, Kastelein RA and Liu YJ (2002) Human epithelial cells trigger dendritic cell-mediated allergic inflammation by producing TSLP. Nature Immunol. 3: 673-680 https://doi.org/10.1038/nrm910
  18. Wang M, Xing ZM, Lu C, Ma YX, Yu DL, Yan Z, Wang SW and Yu LS (2003) A common IL-13 Arg130Gln single nucleotide polymorphism among Chinese atopy patients with allergic rhinitis. Hum. Genet. 113: 387-390 https://doi.org/10.1007/s00439-003-1001-x
  19. Wang YH, Ito T, Wang YH, Homey B, Watanabe N, Martin R, Barnes CJ, McIntyre BW, Gilliet M, Kumar R, Yao Z and Liu YJ (2006) Maintenance and polarization of human Th2 central memory T cells by thymic stromal lymphopoietin-activated dendritic cells. Immunity. 24: 827-838 https://doi.org/10.1016/j.immuni.2006.03.019
  20. Watanabe N, Hanabuchi S, Soumelis V, Yaun W, Ho S, de Waal Malefyt R and Liu YJ (2004) Human thymic stromal lymphopoietin promotes dendritic cell-mediated CD4+ T cell homeostatic expansion. Nature lmmunol. 5: 426-434 https://doi.org/10.1038/ni1048
  21. Ying S, O'Connor B, Ratoff J, Meng Q, Mallett K, Cousins D, Robinson D, Zhang G, Zhao J, Lee TH and Corrigan C (2005) Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity. J. Immunol. 174: 8183-8190 https://doi.org/10.4049/jimmunol.174.12.8183
  22. Yoo J, Omori M, Gyarmati D, Zhou B, Aye T, Brewer A, Comeau MR, Campbell DJ and Zieqler SF (2005) Spontaneous atopic dermatitis in mice expressing an inducible thymic stromal lymphopoietin transgene specifically in the skin. J. Exp. Med. 202: 541-549 https://doi.org/10.1084/jem.20041503