The Wnt5a-Ror2 axis promotes the signaling circuit between interleukin-12 and interferon-γ in colitis.
The Wnt5a-Ror2 axis promotes the signaling circuit between interleukin-12 and interferon-γ in colitis.
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DOI：
10.1038/srep10536
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发表时间：
2015-06-01
影响因子：
4.6
通讯作者：
Kikuchi A
中科院分区：
文献类型：
--
作者：
Sato A;Kayama H;Shojima K;Matsumoto S;Koyama H;Minami Y;Nojima S;Morii E;Honda H;Takeda K;Kikuchi A
Wnt 5a在Wnt信号转导中调节多种细胞功能，参与炎症反应，但其机制尚不清楚。我们使用Wnt 5a及其受体Ror 2的条件性敲除小鼠研究了Wnt 5a信号传导在肠道免疫中的作用。在成年小鼠中去除Wnt 5a或Ror 2抑制葡聚糖硫酸钠（DSS）诱导的结肠炎。它还减弱了DSS依赖性炎症细胞因子产生的增加，并减少了结肠中产生干扰素-γ（IFN-γ）的CD 4 + Th 1细胞数量。在DSS治疗的小鼠和炎症性肠病患者的溃疡性病变中，Wnt 5a在基质成纤维细胞中高度表达。从Wnt 5a和Ror 2缺陷小鼠的结肠中分离的树突状细胞（DC）降低了幼稚CD 4 + T细胞分化为产生IFN-γ的CD 4 + Th 1细胞的能力。体外实验表明，Wnt 5a-Ror 2信号轴增强了IFN-γ对DC的致敏作用，导致脂多糖（LPS）诱导的白细胞介素（IL）-12表达增强。总之，这些结果表明，Wnt 5a促进IFN-γ信号传导，导致DC中的IL-12表达，从而诱导结肠炎中的Th 1分化。
Wnt5a, which regulates various cellular functions in Wnt signaling, is involved in inflammatory responses, however the mechanism is not well understood. We examined the role of Wnt5a signaling in intestinal immunity using conditional knockout mice for Wnt5a and its receptor Ror2. Removing Wnt5a or Ror2 in adult mice suppressed dextran sodium sulfate (DSS)-induced colitis. It also attenuated the DSS-dependent increase in inflammatory cytokine production and decreased interferon-γ (IFN-γ)-producing CD4+ Th1 cell numbers in the colon. Wnt5a was highly expressed in stromal fibroblasts in ulcerative lesions in the DSS-treated mice and inflammatory bowel disease patients. Dendritic cells (DCs) isolated from the colon of Wnt5a and Ror2 deficient mice reduced the ability to differentiate naïve CD4+ T cells to IFN-γ-producing CD4+ Th1 cells. In vitro experiments demonstrated that the Wnt5a-Ror2 signaling axis augmented the DCs priming effect of IFN-γ, leading to enhanced lipopolysaccharide (LPS)-induced interleukin (IL)-12 expression. Taken together, these results suggest that Wnt5a promotes IFN-γ signaling, leading to IL-12 expression in DCs, and thereby inducing Th1 differentiation in colitis.
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影响因子：
64.5
作者：
Gujral TS;Chan M;Peshkin L;Sorger PK;Kirschner MW;MacBeath G
通讯作者：
MacBeath G
影响因子：
5.3
作者：
Keeble, Thomas R.;Halford, Michael M.;Cooper, Helen M.
通讯作者：
Cooper, Helen M.
DOI：
10.1083/jcb.200912128
发表时间：
2010-07-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lin S;Baye LM;Westfall TA;Slusarski DC
通讯作者：
Slusarski DC
影响因子：
4.9
作者：
Karlis, J;Penttila, I;Flesch, IEA
通讯作者：
Flesch, IEA
影响因子：
5.4
作者：
Krajina, T;Leithäuser, F;Reimann, J
通讯作者：
Reimann, J