TY - JOUR
T1 - T helper type 2-biased natural killer cell phenotype in patients with pemphigus vulgaris
AU - Takahashi, Hayato
AU - Amagai, Masayuki
AU - Tanikawa, Akiko
AU - Suzuki, Shigeaki
AU - Ikeda, Yasuo
AU - Nishikawa, Takeji
AU - Kawakami, Yutaka
AU - Kuwana, Masataka
N1 - Funding Information:
We thank Dr Hidemi Toyoda (Mie University) for valuable comments on the evaluation of Stat4 phosphorylation. This study was supported by grants from the Ministry of Education, Sports, Science and Technology and the Ministry of Health, Labour, and Welfare.
PY - 2007/2
Y1 - 2007/2
N2 - 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-12Rβ2, 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.
AB - 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-12Rβ2, 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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U2 - 10.1038/sj.jid.5700527
DO - 10.1038/sj.jid.5700527
M3 - Article
C2 - 16946717
AN - SCOPUS:33846205183
SN - 0022-202X
VL - 127
SP - 324
EP - 330
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 2
ER -