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1: J Invest Dermatol. 2007 Feb;127(2):324-30. Epub 2006 Aug 31.
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T helper type 2-biased natural killer cell phenotype in patients with pemphigus vulgaris.

Takahashi H, Amagai M, Tanikawa A, Suzuki S, Ikeda Y, Nishikawa T, Kawakami Y, Kuwana M.

Department of Dermatology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.

Pemphigus vulgaris (PV) is an autoantibody-mediated bullous disease, but the role of natural killer (NK) cells in its pathogenic process has never been examined in detail. Circulating CD56+ CD3- NK cells as well as CD69+-activated NK cells were increased in PV patients compared with healthy controls and patients with other autoantibody-mediated autoimmune diseases, including immune thrombocytopenic purpura and myasthenia gravis. Gene expression analysis of highly purified NK cells demonstrated an increased expression of IL-10 and decreased expression of IL-12Rbeta2, perforin, and granzyme B ex vivo in PV patients versus healthy controls. The NK cells from PV patients also showed impaired signal transducer and activator of transduction4 phosphorylation upon in vitro IL-12 stimulation. Moreover, NK cells from PV patients exhibited reduced IL-10 production in response to in vitro stimulation with IL-2/IL-12. Finally, IL-5 expression in NK cells was exclusively detected ex vivo in PV patients with active disease, and was lost in subsequent analyses performed during disease remission. Together these findings suggest that NK cells contribute to a T helper type 2-biased immune response in PV patients through impaired IL-12 signaling and an upregulation of IL-10 and IL-5.

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PMID: 16946717 [PubMed - indexed for MEDLINE]