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Journal of Clinical Immunology

Published in:

01-10-2011

Altered Peripheral Invariant Natural Killer T Cells in Atopic Dermatitis

Authors: Edit Gyimesi, Georgina Nagy, Éva Remenyik, Sándor Sipka, Margit Zeher, Tamás Bíró, Andrea Szegedi

Published in: Journal of Clinical Immunology | Issue 5/2011

Abstract

Background

Conflicting data exist on the number of invariant NKT (iNKT) cells in atopic dermatitis (AD); furthermore, no data have been published on their functional capacity.

Methods

The frequency and number of circulating CD3+6B11+ iNKT cells and their CD4+ and CD4− subpopulations were evaluated in peripheral blood obtained from 41 patients with AD by four-color flow cytometry. Likewise, functional properties of iNKT cells were measured by five-color intracellular cytokine staining.

Results

The number and percentage of total iNKT cells and their CD4/CD8 subpopulations were significantly lower than the controls. Of further importance, the CD4−CD8− (double negative, DN) iNKT subgroup showed the strongest positive correlation with total iNKT cells. In addition, the DN subgroup exhibited the most pronounced functional alteration with significantly decreased levels of intracellular IFNγ and significantly increased levels of intracellular IL-4 in AD patients compared with the controls.

Conclusion

The significantly altered number and cytokine production of iNKT cells from AD patients suggests that these cells may play an important role in the pathogenesis of AD.

Boguniewitz M, Leung DYM. Atopic dermatitis. J Allergy Clin Immunol. 2008;117:S475–80.CrossRef

Bieber T. Atopic dermatitis. Ann Dermatol. 2010;22:125–37.PubMedCrossRef

Grewe M, Brujnzeel-Koonen C, Schöpf E, Thepen T, Langeveld-Wildschut AG, Ruzicka T, et al. A role for Th1 and Th2 cells in the immunopathogenesis of atopic dermatitis. Immunol Today. 1998;19:359–61.PubMedCrossRef

Szegedi A, Baráth S, Nagy G, Szodoray P, Gál 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;160:984–93.PubMedCrossRef

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 T_H17 T cells. J Allergy Clin Immunol. 2009;123:1244–52.PubMedCrossRef

Koga C, Kabashima K, Shiraishi N, Kobayashi M, Tokura Y. Possible Pathogenic role of Th17 cells for atopic dermatitis. J Investig Dermatol. 2008;128:2625–30.PubMedCrossRef

De Benedetto A, Agnihothri R, McGirt LY, Bankova LG, Beck LA. Atopic dermatitis: a disease caused by innate immune defects? J Invest Dermatol. 2009;129:14–30.PubMedCrossRef

Cork MJ, Danby SG, Vasilopoulos Y, Hadgraft J, Lane ME, Moustafa M, et al. Epidermal dysfunction in atopic dermatitis. J Invest Dermatol. 2009;129:1892–908.PubMedCrossRef

Godfrey DI, Kronenberg M. Going both ways: immune regulation via CD1d-dependent NKT cells. J Clin Invest. 2004;114:1379–87.PubMed

10.

Kronenberg M, Gapin L. The unconventional lifestyle of NKT cells. Nat Rev Immunol. 2002;2:557–68.PubMed

11.

Bendelac A, Rivera MN, Park SH, Roark JH. Mouse CD1-specific NK1 T cells: development, specificity, and function. Annu Rev Immunol. 1997;15:535–62.PubMedCrossRef

12.

Porcelli S, Yockey CE, Brenner AB, Balk SP. Analysis of T cell antigen receptor (TCR) expression by human peripheral blood CD4-8-alpha/beta T cells demonstrates preferential use of several V beta genes and an invariant TCR alpha chain. J Exp Med. 1993;178:1–16.PubMedCrossRef

13.

Godfrey D, Hammond K, Poulton L, Smyth M, Baxter A. NKT cells: facts, functions and fallacies. Immunol Today. 2000;21:573–83.PubMedCrossRef

14.

Exley M, Garcia J, Balk SP, Porcelli S. Requirements for CD1d recognition by human invariant Valpha24+ CD4-CD8- T cells. J Exp Med. 1997;186:109–20.PubMedCrossRef

15.

Balato A, Unutmaz D, Gaspari AA. Natural killer T cells: An unconventional T-cell subset with diverse effector and regulatory functions. J Investig Dermatol. 2009;129:1628–42.PubMedCrossRef

16.

Van Kaer L, Parekh VV, Wu L. Invariant natural killer T cells: bridging innate and adaptive immunity. Cell Tissue Res. 2011;343:43–55.PubMedCrossRef

17.

Taniguchi M, Harada M, Kojo S, Nakayama T, Wakao H. The regulatory role of Valpha14 NKT cells in innate and acquired immune response. Annu Rev Immunol. 2003;21:483–513.PubMedCrossRef

18.

Wu L, Van Kaer. Natural killer T cells and autoimmune disease. Curr Mol Med. 2009;9:4–14.PubMedCrossRef

19.

Van der Vliet HJ, von Blomberg ME, Nishi N, Reijm M, Voskuyl AE, van Bodegraven A, et al. Circulating Vα24 + Vβ11+ NKT cell numbers are decreased in a wide variety of diseases that are characterized by autoreactive tissue dammage. Clin Immunol. 2001;100:144–8.PubMedCrossRef

20.

Sumida T, Sakamoto H, Murata A, Makino Y, Takahashi H, Yoshida S, et al. Selective reduction in T cells bearing invariant V alpha 24 J alpha Q antigen receptor in patients with systemic sclerosis. J Exp Med. 1995;182:1163–8.PubMedCrossRef

21.

Godó M, Sessler T, Hamar P. Role of invariant natural killet T (iNKT) cells in systemic lupus erythematosus. Curr Med Chem. 2008;15:1778–87.PubMedCrossRef

22.

Novak J, Griseri T, Beaudoin L, Lehuen A. Regulation of type 1 diabetes by NKT cells. Int Rev Immunol. 2007;26:49–72.PubMedCrossRef

23.

Simon D, Kozlowski E, Simon H. Natural killer T cells expressing IFN-gamma and IL-4 in lesional skin of atopic eczema. Allergy. 2009;64:1681–4.PubMedCrossRef

24.

Gober MD, Fishelevich R, Zhao Y, Unutmaz D, Gaspari AA. Human natural killer T cells infiltrate into the skin at elicitation sites of allergic contact dermatitis. J Invest Dermatol. 2008;128:1460–9.PubMedCrossRef

25.

Takahashi T, Nakamura K, Chiba S, Kanda Y, Tamaki K, Hirai H. Vα24+ natural killer T cells are markedly decreased in atopic dermatitis patients. Hum Immunol. 2003;64:586–92.PubMedCrossRef

26.

Magnan A, Mély L, Prato S, Vervloet D. Relationships between natural T cells, atopy, IgE levels, and IL-4 production. Allergy. 2000;55:286–90.PubMedCrossRef

27.

Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol Suppl. 1980;92:44–7.

28.

Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European task force on Atopic Dermatitis. Dermatology. 186: 29–31, 1993

29.

Wolkerstorfer A, de Waard van der Spek FB, Glazenburg EJ, Mulder PG, Oranje AP. Scoring the severity of atopic dermatitis: three item severity score as a rough system for daily practice and as a pre-screening tool for studies. Acta Derm Venereol. 1999;79:356–9.PubMedCrossRef

30.

Montoya CJ, Pollard D, Martinson K, Kumari K, Wasserfall C, Mulder CB, et al. Characterization of human invariant natural killer T subsets in health and disease using a novel invariant natural killer T cell-clonotypic monoclonal antibody, 6B11. Immunology. 2007;122:1–14.PubMedCrossRef

31.

Umetsu DT, DeKruyff RH. Natural killer T cells are important in the pathogenesis of asthma: the many pathways to asthma. J Allergy Clin Immunol. 2010;125:975–9.PubMedCrossRef

32.

Akbari O, Faul JL, Hoyte EG, Berry GJ, Wahlstrom J, Kronenberg M, et al. CD4+ invariant T-cell-receptor + natural killer T cells in bronchial asthma. N Engl J Med. 2006;354:1117–29.PubMedCrossRef

33.

Vijayanand P, Seumois G, Pickard C, Gadola SD, Friedmann PS, Djukanovicz R. Invariant natural killer T cells in asthma and chronic obstructive pulmonary disease. N Engl J Med. 2007;356:1410–22.PubMedCrossRef

34.

Gumperz JE, Miyake S, Yamamura T, Brenner MB. Functionally distinct subsets of CD1d-restricted natural killer T cells revealed by CD1d tetramer staining. J Exp Med. 2002;195:625–36.PubMedCrossRef

35.

Metelitsa LS. Flow cytometry for natural killer T cells: multiparameter methods for multifunctional cells. Clin Immunol. 2004;110:267–76.PubMedCrossRef

36.

Jing Y, Gravenstein S, Chaganty NR, Chen N, Lyerly KH, Joyce S, et al. Aging is associated with a rapid decline in frequency, alterations in subset composition, and enhanced Th2 response in CD1d-restricted NKT cells from human peripheral blood. Exp Gerontol. 2007;42:719–32.PubMedCrossRef

37.

Molling JW, Kölgen W, van der Vliet HJ, Boomsman MF, Kruizenga H, Smorenburg CH, et al. Peripheral blood IFN-γ-secreting Vα24 + Vβ + NKT cell numbers are decreased in cancer patients independent of tumor type or tumor load. Int J Canc. 2005;116:87–93.CrossRef

38.

Davodeau F, Peyrat MA, Necker A, Dominici R, Blanchard F, Leget C, et al. Close phenotypic and functional similarities between human and murine alphabeta T cells expressing invariant TCR alpa-chains. J Immunol. 1997;158:5603–11.PubMed

39.

Prussin C, Foster B. TCR V alpha 24 and V beta 11 coexpression defines a human NK1 T cell analog containing a unique Th0 subpopulation. J Immunol. 1997;159:5862–70.PubMed

40.

Ilhan F, Kandi B, Akbulut H, Turgut D, Cicek D. Atopic dermatitis and Valpha24+ natural killer T cells. Skinmed. 2007;6:218–20.PubMedCrossRef

41.

Oishi Y, Sakamoto A, Nakajama H, Nakao A, Nakagawa N, Tanabe E, et al. CD4-CD8- T cells bearing invariant Vα24JαQ TCR α-chain are decreased in patients with atopic diseases. Clin Exp Immunol. 2000;119:404–11.PubMedCrossRef

42.

Prell C, Konstantopoulos N, Heinzelmann B, Frankenberger B, Reinhard D, Schendel D, et al. Frequency of Vα24⁺CD161⁺ natural killer T cells and invariant TCRAV24-AJ18 transcripts in atopic and non-atopic individuals. Immunobiology. 2003;280:367–80.CrossRef

43.

Wu WH, Park CO, Oh SH, Kim HJ, Kwon YS, Bae BG, et al. Thymic stromal lymphopoietin-acivated natural killer T cells trigger an innate allergic immune response in atopic dermatitis. J Allergy Clin Immunol. 2010;126:290–9.PubMedCrossRef

44.

Croudace JE, Curbishley SM, Mura M, Wilcox CR, Illarionov PA, Besra GS, et al. Identification of distinct human invariant natural killer T-cell response phenotypes to alpha-galactosylceramide. BMC Immunol. 2008;9:71.PubMedCrossRef

45.

Im JS, Kang TJ, Lee SB, Kim CH, Lee SH, Venkataswamy MM, et al. Alteration of the relative levels of iNKT cell subsets is associated with chronic mycobacterial infections. Clin Immunol. 2008;127:214–24.PubMedCrossRef

46.

Lind SM, Kuylenstierna C, Moll M, Jordö ED, Winquist O, Lundenberg L, et al. IL-18 skews the invariant NKT-cell population via autoreactive activation in atopic eczema. Eur J Immunol. 2009;39:2293–301.PubMedCrossRef

47.

Seino K, Taniguchi M. Functionally distinct NKT cell subsets and subtypes. J Exp Med. 2005;202:1623–6.PubMedCrossRef

48.

Lee PT, Benlagha K, Teyton L, Bendelac A. Distinct functional lineages of Vα24 natural killer T cells. J Exp Med. 2002;195:637–41.PubMedCrossRef

49.

Arrenberg P, Halder R, Kumar V. Cross-regulation between distinct natural killer T cell subsets influences immune response to self and foreign antigens. J Cell Physiol. 2009;218:246–50.PubMedCrossRef

50.

Wang Z, Kusam S, Munugalavadla V, Kapur R, Brutkievicz RR, Dent AL. Regulation of Th2 cytokine expression in NKT cells: Unconventional use of Stat6, Gata-3, and NFAT2. J Immunol. 2006;176:880–8.PubMed

51.

Aleksza M, Lukács A, Antal-Szalmás P, Hunyadi J, Szegedi A. Increased frequency of intracellular interleukin (IL)-13 and IL-10, but not IL-4, expressing CD4+ and CD8+ peripheral T cells of patients with atopic dermatitis. Br J Dermatol. 2002;147:1135–41.PubMedCrossRef

Title: Altered Peripheral Invariant Natural Killer T Cells in Atopic Dermatitis
Authors: Edit Gyimesi
Georgina Nagy
Éva Remenyik
Sándor Sipka
Margit Zeher
Tamás Bíró
Andrea Szegedi
Publication date: 01-10-2011
Publisher: Springer US
Published in: Journal of Clinical Immunology / Issue 5/2011
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-011-9551-5

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