Thymic stromal lymphopoietin-activated invariant natural killer T cells trigger an innate allergic immune response in atopic dermatitis.
BACKGROUND
Although invariant natural killer T (iNKT) cells have been shown to play a critical role in the pathogenesis of asthma, the role of iNKT cells in atopic dermatitis (AD) has not been well evaluated.


OBJECTIVE
We investigated whether iNKT cells in patients with AD increased and whether iNKT cells were activated by thymic stromal lymphopoietin (TSLP), which is highly expressed in keratinocytes of AD.


METHODS
We assessed the population of iNKT cells in PBMCs of patients with AD and healthy controls (HCs) using flow cytometry. Immunohistochemistry was used to evaluate iNKT cells and TSLP expression in AD and HC skin. We also evaluated whether iNKT cells expressed the TSLP receptor, the effects of TSLP on iNKT cells, and iNKT cell-dendritic cell interactions in a TSLP-rich environment.


RESULTS
There were more iNKT cells among PBMCs of patients with moderate to severe AD than mild AD (P < .05) and HC (P < .001). The number of iNKT cells was significantly larger in severe AD skin lesions than in mild (P < .001) or moderate AD skin lesions (P < .05). TSLP expression increased in lesional skin (P < .001) but not in the sera of patients with AD (P = .729) compared with HC. iNKT cells expressed TSLP receptor protein and mRNA. TSLP directly activated iNKT cells to secrete IL-4 and IL-13, and the concurrent addition of dendritic cells further activated IFN-gamma expression.


CONCLUSIONS
Increased iNKT cells activated by TSLP, especially in patients with severe AD, might play an essential role in the innate allergic immune response in AD.
Wu
Wen Hao
WH
Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
Park
Chang Ook
CO
Oh
Sang Ho
SH
Kim
Hee Jung
HJ
Kwon
Yeon Sook
YS
Bae
Byung Gi
BG
Noh
Ji Yeon
JY
Lee
Kwang Hoon
KH
D000328:Adult; D002450:Cell Communication / Q000276:immunology; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018121:Receptors, Cytokine / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000094632:Thymic Stromal Lymphopoietin
C498762:CRLF2 protein, human; D016207:Cytokines; D018121:Receptors, Cytokine; D000094632:Thymic Stromal Lymphopoietin