Original Article
 

House Dust Mites Confer a Distinct Immunological Feature among Dermatitis

Abstract

Atopic dermatitis (AD) is a heterogeneous disease with regard to clinical phenotype and natural history. We investigated T cell subtypes and cytokine responses in peripheral blood and skin lesions of AD patients with various sensitivities. Immunological studies were performed in 27 subjects: 9 house dust mite (HDM)-sensitized; 6 subjects with sensitizations other than HDM; 7 non-allergic AD patients and 5 healthy controls. Among those, skin biopsy samples of 13 subjects were evaluated for immunohistochemical analyses, as well. The mean age was 8.93±5.17 years. HDM-allergic AD emerged as a distinct immunologic phenotype, with higher production of interleukin (IL)-4, -5, -2 both at rest and when stimulated by Der p1 or SEB along with higher Th17. As for TH17 cell percentage, it was increased in all AD groups compared to healthy controls, while HDM-allergic group was distinguished with a significantly lower production of IL-17. Patients with sensitizations other than HDM were mostly similar to non-allergic AD, with increased Th17 and CD4+CD69+interferon-gamma (IFN-γ)+ T cells percentage. The biopsy of lesional skin showed that HDM-allergic AD had lower IFN-γ and IFN-γ co-expressing CD8+ T cells compared to patients with other sensitizations (p=0.03 and p=0.04, respectively). Among the HDM allergic patients, pairwise comparison of lesional versus non-lesional skin revealed higher CD4+ T cells numbers, expression of forkhead box P3 (Foxp3) and T-cell-specific transcription factor (T-bet) (p=0.018, p=0.018, p=0.018, respectively). HDM-allergic AD is a distinct subtype with a predominant skewing in Th2 and higher Th17 cell percentage along with a blunted Th1 response in the skin, all of which may have therapeutic implications.

1. Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee Sp, et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 2006;38(4):441-6.

2. Rodríguez-Orozco AR, Kanán-Cedeño EG, Guillén Martínez E, Campos Garibay MJ. Family functioning and illness perception of parents of children with atopic dermatitis, living without skin symptoms, but with psychosomatic symptoms. Iran J Allergy Asthma Immunol 2011; 10(1):61-5.

3. Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA. New insights into atopic dermatitis. J Clin Invest 2004; 113(5):651-7.

4. Boniface K, Bernard FX, Garcia M, Gurney AL, Lecron JC, Morel F. IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes. J Immunol 2005; 174(6):3695-702.

5. Guttman-Yassky E, Nograles KE, Krueger JG.Contrasting pathogenesis of atopic dermatitis and psoriasis-part II: immune cell subsets and therapeutic concepts. J Allergy Clin Immunol 2011; 127(6):1420-32.

6. Dai X, Sayama K, Tohyama M, Shirakata Y, Hanakawa Y, Tokumaru S, et al. Mite allergen is a danger signal for the skin via activation of inflammasome in keratinocytes. J Allergy Clin Immunol 2011; 127(3):806-14.

7. Nograles KE, Zaba LC, Shemer A, Fuentes-Duculan J, Cardinale I, Kikuchi T, et al. IL-22-producing ‘‘T22’’ T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells. J Allergy Clin Immunol 2009; 123(6):1244-52.

8. Guttman-Yassky E, Lowes MA, Fuentes-Duculan J, Zaba C, Cardinale I, Nograles KE, et al. Low expression of the IL-23/Th17 pathway in atopic dermatitis compared to psoriasis. J Immunol 2008; 181(10):7420-27.

9. Koga C, Kabashima K, Shiraishi N, Kobayashi M, Tokura

Y. Possible pathogenic role of Th17 cells for atopic dermatitis. J Invest Dermatol 2008; 128(11):2625-30.

10. Hanifin JM, Chan SC, Cheng JB, Tofte SJ, Henderson WR Jr, Kirby DS, Weiner ES. Type 4 phosphodiesterase inhibitors have clinical and in vitro anti-inflammatory effects in atopic dermatitis. J Invest Dermatol 1996;107(1):51-6.

11. Novak N, Leung DY. Advances in atopic dermatitis. Curr Opin Immunol 2011; 23(6):778-83.

12. Bieber T. Atopic dermatitis. N Engl J Med 2008;358(14):1483-94.

13. Leung DY, Bieber T. Atopic dermatitis. Lancet 2003;361(9352):151-60.

14. Elias PM, Schmuth M. Abnormal skin barrier in the etiopathogenesis of atopic dermatitis. Curr Opin Allergy Clin Immunol 2009; 9(5):437-46.

15. Elias PM, Steinhoff M. ‘‘Outside-to-inside’’ (and now back to ‘‘outside’’) pathogenicmechanisms in atopic dermatitis. J Invest Dermatol 2008; 128(5):1067-70.

16. Guttman-Yassky E, Nograles KE, Krueger JG.Contrasting pathogenesis of atopic dermatitis and psoriasis--part I: clinical and pathologic concepts. J Allergy Clin Immunol 2011; 127(5):1110-18.

17. Chapman MD, Wunschmann S, Pomes A. Proteases as Th2 adjuvants. Curr Allergy Asthma Rep 2007; 7(5):363-7.

18. Kikuchi Y, Takai T, Kuhara T, OtaM, Kato T, Hatanaka H, et al. Crucial commitment of proteolytic activity of a purified recombinant major house dust mite allergen Der p 1 to sensitization toward IgE and IgG responses. J Immunol 2006; 177(3):1609-17.

19. Gough L, Schulz O, Sewell HF, Shakib F. The cysteine protease activity of the major dust mite allergen Der p 1 selectively enhances the immunoglobulin E antibody response. J Exp Med 1999; 190(12):1897-902.

20. Wan H, Winton HL, Soeller C, Tovey ER, Gruenert DC, Thompson PJ, et al. Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions. J Clin Invest 1999; 104(1):123-33.

21. Nakamura T, Hirasawa Y, Takai T, Mitsuishi K, Okuda M, Kato T, et al. Reduction of skin barrier function by proteolytic activity of a recombinant house dust mite major allergen Der f 1. J Invest Dermatol 2006;126(12):2719-23.

22. Shakib F, Schulz O, Sewell H. A mite subversive:cleavage of CD23 and CD25 by Der p 1 enhances allergenicity. Immunol Today 1998; 19(7):313-6.

23. Wan H, Winton HL, Soeller C, Taylor GW, Gruenert DC Thompson PJ, et al. The transmembrane protein ccluding of epithelial tight junctions is a functional target for serine peptidases from faecal pellets of Dermatophagoides pteronyssinus. Clin Exp Allergy 2001;31(2):279-94.

24. Sun G, Stacey MA, Schmidt M, Mori L, Mattoli S.Interaction of mite allergens Derp3 and Derp9 with protease-activated receptor-2 expressed by lung epithelial cells. J Immunol 2001; 167(2):1014-21.

25. Seto T, Takai T, Ebihara N, Matsuoka H, Wang XL, Ishii A, et al. SLPI prevents cytokine release in mite protease exposed conjunctival epithelial cells. Biochem Biophys Res Commun 2009; 379(3):681-5.

26. Cormican L, O’Sullivan S, Burke CM, Poulter LW. IFN- gamma but not IL-4 T cells of the asthmatic bronchial wall show increased incidence of apoptosis. Clin Exp Allergy 2001; 31(5):731-9.

27. Akkoc T, de Koning PJ, Ruckert B, Barlan I, Akdis M, Akdis CA. Increased activation-induced cell death of high IFN-gamma-producing T(H)1 cells as a mechanism of T(H)2 predominance in atopic diseases. J Allergy Clin Immunol 2008; 121(3):652-8.

28. Akdis M, Trautmann A, Klunker S, Daigle I, Kucuksezer UC, Deglmann W, et al. T helper (Th) 2 predominance in atopic diseases is due to preferential apoptosis of circulating memory/effector Th1 cells. FASEB J 2003;17(9):1026-35.

29. Weidinger S, Novak N. Atopic dermatitis. Lancet 2015;387(10023):1109-22.

30. Toda M, Leung DY, Molet S, Boguniewicz M, Taha R, Christodoulopoulos P, et al. Polarized in vivo expression of IL-11 and IL-17 between acute and chronic skin lesions. J Allergy Clin Immunol 2003; 111(4):875-81.

31. Eyerich K, Pennino D, Scarponi C, Foerster S, Nasorri F,Behrendt H, et al. IL-17 in atopic eczema: linking allergen-specific adaptive and microbial-triggered innate immune response. J Allergy Clin Immunol 2009;123(1):59-66.

32. Caproni M, Antiga E, Torchia D, Volpi W, Barletta E, Gitti G, et al. FoxP3-expressing T regulatory cells in atopic dermatitis lesions. Allergy Asthma Proc 2007;28(5):525-8.

33. Szegedi A, Barath S, Nagy G, Szodoray P, Gal M, Sipka S, et al. Regulatory T cells in atopic dermatitis: epidermal dendritic cell clusters may contribute to their local expansion. Br J Dermatol 2009; 160(5):984-93.

34. Schnopp C, Rad R, Weidinger A, Weidinger S, Ring J, Eberlein B, et al. Fox-P3-positive regulatory T cells are present in the skin of generalized atopic eczema patients and are not particularly affected by medium-dose UVA1 therapy. Photodermatol Photoimmunol Photomed 2007;23(2-3):81-5.

35. Lin YT, Wang CT, Chao PS, Lee JH, Wang LC, Yu HH, et al. Skin-homing CD4+ Foxp3+ T cells exert Th2-like function after staphylococcal superantigen stimulation in atopic dermatitis patients. Clin Exp Allergy 2011;41(4):516-25.

36. Gros E, Petzold S, Maintz L, Bieber T, Novak N.Reduced IFN-γ receptor expression and attenuated IFN-γ response by dendritic cells in patients with atopic dermatitis. J Allergy Clin Immunol 2011; 128(5):1015-21.

37. Novak N, Bieber T, Hoffmann M, Fölster-Holst R, Homey B, Werfel T, et al. Efficacy and safety of subcutaneous allergen-specific immunotherapy with epigmented polymerized mite extract in atopic dermatitis. J Allergy Clin Immunol 2012; 130(4):925-31.

38. Boguniewicz M, Jaffe HS, Izu A, Sullivan MJ, York D, Geha RS, et al. Recombinant gamma interferon in treatment of patients with atopic dermatitis and elevated IgE levels. Am J Med 1990; 88(4):365-70.

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IssueVol 15, No 4 (2016) QRcode
SectionOriginal Article(s)
Keywords
Atopic dermatitis House dust mite Interferon-gamma Skin lesion Th17 Cells

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How to Cite
1.
Baris S, Ozen A, Akdeniz T, Karakoc-Aydiner E, Aydin O, Ercan H, Ogulur I, Camcioglu Y, Cengizlier R, Demirkesen C, Yucelten D, Demirel G, Barlan I. House Dust Mites Confer a Distinct Immunological Feature among Dermatitis. Iran J Allergy Asthma Immunol. 2016;15(4):264-274.