Interferon-γ-deficient mice are resistant to the development of alopecia areata
Interferon-γ-deficient mice are resistant to the development of alopecia areata
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DOI：
10.1111/j.1365-2133.2006.07377.x
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发表时间：
2006-09-01
影响因子：
10.3
通讯作者：
Zoeller, M.
中科院分区：
文献类型：
--
作者：
Freyschmidt-Paul, P.;McElwee, K. J.;Zoeller, M.
背景：斑秃（AA）是一种T细胞介导的毛囊自身免疫性疾病，可通过CD4+ T细胞转移。然而，是否辅助性t细胞因子（Th） 1或Th2细胞因子占优势尚未确定。方法：为了阐明Th1细胞在AA发病机制中的重要作用，我们研究了干扰素(IFN)- γ在AA实验诱导中的功能作用。结果：将AA影响的C3H/HeJ小鼠全层皮肤移植到C3H/HeJ小鼠上，靶向缺失Th1细胞因子IFN- γ基因（IFN γ(-/-)）和移植到野生型小鼠（IFN γ(+/+)）上，实验诱导AA。结果：虽然90%的野生型小鼠发生AA，但没有IFN γ(-/-)小鼠出现脱发。对照组皮肤切片免疫组化显示CD4+和CD8+ T细胞在滤泡周围和滤泡内密集浸润，而IFN γ(-/-)小鼠皮肤浸润性CD8+ T细胞缺失，CD4+细胞数量明显减少。主要组织相容性复合体I类和II类分子在假定的免疫特权毛囊基底下部位的异常表达在AA抗性IFN γ(-/-)小鼠中比在AA对照小鼠中更弱。流式细胞术显示，IFN γ(-/-)小鼠的白细胞对aa影响皮肤的转移没有反应。与IFN γ(+/+)小鼠不同的是，在aa抗性IFN γ(-/-)小鼠的引流淋巴结细胞或皮肤浸润白细胞中，t细胞激活标记物和Th1细胞因子均未上调。然而，在IFN γ(-/-)小鼠中，没有证据表明Th2细胞因子谱的变化，也没有证据表明调节性T细胞的上调。结论：IFN γ(-/-)小鼠对移植的（自身）抗原没有激活Th1细胞，这表明IFN γ介导的Th1激活是诱导AA的必要条件。
Background: Alopecia areata (AA) is a T-cell mediated putative autoimmune disease of hair follicles, which can be transferred by CD4+ T cells. However, whether T-helper (Th) 1 or Th2 cytokines are predominant has not yet been defined.Methods: To elucidate the importance of Th1 cells in the pathogenesis of AA we investigated the functional role of interferon (IFN)-gamma in the experimental induction of AA.Results: AA was experimentally induced by grafting full-thickness skin from AA-affected C3H/HeJ mice on to C3H/HeJ mice with a targeted deletion of the Th1 cytokine IFN-gamma gene (IFN gamma(-/-)) and on to wild-type mice (IFN gamma(+/+)).Results: While 90% of wild-type mice developed AA, none of the IFN gamma(-/-) mice exhibited hair loss. Immunohistochemistry of skin sections revealed a dense perifollicular and intrafollicular infiltrate of CD4+ and CD8+ T cells in controls, while in IFN gamma(-/-) mice skin-infiltrating CD8+ T cells were absent and the number of CD4+ cells was significantly reduced. Aberrant expression of major histocompatibility complex class I and II molecules in the putative immune-privileged infrainfundibular site of the hair follicle was found to be weaker in AA-resistant IFN gamma(-/-) mice than in control mice with AA. Flow cytometry revealed that leucocytes of IFN gamma(-/-) mice did not respond to the transfer of AA-affected skin. As distinct from IFN gamma(+/+) mice, neither T-cell activation markers nor Th1 cytokines were upregulated in draining lymph node cells or skin-infiltrating leucocytes of AA-resistant IFN gamma(-/-) mice. However, there was no evidence for a shift towards a Th2 cytokine profile, nor for upregulation of regulatory T cells in IFN gamma(-/-) mice.Conclusions: IFN gamma(-/-) mice fail to activate Th1 cells in response to the transplanted (auto)antigens, which suggests an essential requirement for IFN-gamma-mediated Th1 activation in the induction of AA.