A role for TGF beta 1 in Langerhans cell biology - Further characterization of the epidermal Langerhans cell defect in TGF beta 1 null mice
A role for TGF beta 1 in Langerhans cell biology - Further characterization of the epidermal Langerhans cell defect in TGF beta 1 null mice
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DOI：
10.1172/jci119567
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发表时间：
1997-08-01
影响因子：
15.9
通讯作者：
Udey, MC
中科院分区：
文献类型：
--
作者：
Borkowski, TA;Letterio, JJ;Udey, MC
先前对TGF β 1缺失（-/-）小鼠的研究表明，表皮缺乏朗格汉斯细胞（LC），并且LC缺乏不是继发于炎症，而炎症是-/-表型的主要特征（Borkowski， T.A， J.J. Letterio， A.G. Farr和M.C. Udey, 1996）。医学杂志。184:2417-2422)。在此，我们证明了树突状细胞可以从-/-小鼠和同窝对照的骨髓中扩增出来。来自-/-小鼠的骨髓在移植到受致死性辐射的受体后也产生LC。因此，TGF β 1缺失小鼠的LC缺陷不是由于骨髓前体的绝对缺乏，分泌旁分泌TGF β 1足以促进LC的发展。我们使用了几种方法来评估-/-皮肤对LC定位的适用性。一项调查显示，尽管许多细胞因子mrna是从头表达的，但编码促炎细胞因子的mrna在-/-皮肤中并没有显著的过度表达，这些mrna已知可以从表皮调动LC （IL-1和TNF - α）。此外，移植到BALB/c nu/nu受体后，骨髓来源的LC填充了全层TGF β 1缺失皮肤。最后，表达截断的loricrin启动子驱动的显性阴性TGF β II型受体的转基因小鼠皮肤含有正常数量的LC。由于这些小鼠的TGF β 1信号仅在角化细胞中被破坏，并且TGF β 1 -/-表型的角化细胞超增殖成分被复制，这些结果强烈表明TGF β 1缺失小鼠的LC缺陷不是由于表皮异常，而是反映了小鼠LC（或其前体）对TGF β 1的需求。
Previous studies of TGF beta 1 null (-/-) mice indicated that the epidermis was devoid of Langerhans cells (LC) and that the LC deficiency was not secondary to the inflammation that is the dominant feature of the -/- phenotype (Borkowski, T.A., J.J. Letterio, A.G. Farr, and M.C. Udey. 1996. J. Exp. Med. 184:2417-2422). Herein, we demonstrate that dendritic cells could be expanded from the bone marrow of -/- mice and littermate controls. Bone marrow from -/- mice also gave rise to LC after transfer into lethally irradiated recipients. Thus, the LC defect in TGF beta 1 null mice does not result from an absolute deficiency in bone marrow precursors, and paracrine TGF beta 1 production is sufficient for LC development. Several approaches were used to assess the suitability of -/- skin for LC localization. A survey revealed that although a number of cytokine mRNAs were expressed de novo, mRNAs encoding proinflammatory cytokines known to mobilize LC from epidermis (IL-1 and TNF alpha) were not strikingly overrepresented in -/- skin. In addition, bone marrow-derived LC populated full-thickness TGF beta 1 null skin after engraftment onto BALB/c nu/nu recipients, Finally, the skin of transgenic mice expressing a truncated loricrin promoter-driven dominant-negative TGF beta type II receptor contained normal numbers of LC. Because TGF beta 1 signaling in these mice is disrupted only in keratinocytes and the keratinocyte hyperproliferative component of the TGF beta 1 -/- phenotype is reproduced, these results strongly suggest that the LC defect in TGF beta 1 null mice is not due to an epidermal abnormality but reflects a requirement of murine LC (or their precursors) for TGF beta 1.