Interleukin-29: Just an extra string in the bow of Th17 cells or a target for therapeutic exploitation?
Interleukin-29: Just an extra string in the bow of Th17 cells or a target for therapeutic exploitation?
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Interleukin-29：只是 Th17 细胞弓上的一根额外的绳子还是治疗开发的目标？
DOI：
10.1007/s00109-016-1412-5
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Johnston,Andrew
中科院分区：
文献类型：
--
作者：
Johnston,Andrew
在这个问题上，Witte及其同事描述了IL-29（一种III型干扰素）诱导角质形成细胞表达CXCL 9、CXCL 10和CXCL 11的能力，这三种趋化因子与活化的Th 1 T细胞进入炎症部位的运输有关[1]。鉴于Th 17细胞可能是IL-29的主要来源，这一发现既加强了Th 17细胞在抗病毒防御中的作用，也可能有助于解释在银屑病（一种常见的炎症性皮肤病）中观察到的混合Th 1/Th 17表型。肠道、肺和皮肤的上皮屏障处的免疫能力需要上皮细胞自身、抗体、补体以及驻留和浸润免疫细胞的协同努力，以便能够对潜在病原微生物的屏障破坏和入侵做出及时反应。T细胞在上皮细胞中发挥重要的防御作用，非再循环组织驻留记忆T细胞提供针对屏障组织中最常见的病原体的快速特异性免疫保护，由先天免疫细胞和循环T细胞支持，可根据需要调用[2，3]。在组织内具有大量全副武装的T细胞的一个权衡是这些细胞的失控或失调可以引发和维持慢性自身免疫性和炎性疾病，例如克罗恩病，多发性硬化症和牛皮癣。在过去的十年中，Thl 7细胞的贡献已被认为是上皮屏障处免疫的重要方面[4];然而，Thl 7细胞和IL-17 A也与它们的许多病理学有关[5] JL-17 A是上皮表达抗微生物蛋白和肽的有效诱导剂。在皮肤中，IL-17 A与几种细胞因子（包括IFN-γ [6]和TNF-α [7]）协同作用，有效地诱导一系列抗菌肽和蛋白质，包括S100 A7、A8和A9、凯萨林菌素LL-37和人β-防御素（HBD）-2，3和4。协同工作，这些抗菌肽提供了广谱的抗菌活性，并且也已被证明对某些病毒具有功效[8]。除了它们的抗微生物活性之外，防御素还在先天性和获得性免疫的调节中起作用。HBD-2、3和4诱导促炎细胞因子表达（IL-6、CXCL 10、CCL 2、CCL 5和CCL 20）以及角质形成细胞的迁移和增殖，促进伤口愈合[9]。HBD-2也是巨噬细胞、肥大细胞、活化的中性粒细胞、记忆T细胞和树突状细胞（DC）的化学引诱物[10]。匡威亦然：当以足够高的浓度使用时，趋化因子如CCL 20已被证明具有抗微生物活性[11]。
In this issue, Witte and colleagues describe the ability of IL-29, a type III interferon, to induce keratinocyte expression of CXCL9, CXCL10 and CXCL11, three chemokines implicated in the trafficking of activated Th1 T cells into sites of inflammation [1]. Given that Th17 cells may be the principal source of IL-29, this finding both strengthens the role of Th17 cells in antiviral defenses and may help explain the mixed Th1/Th17 phenotype seen in psoriasis, a common inflammatory skin disease. Immune competence at the epithelial barriers of the gut, lungs and skin takes a concerted effort from the epithelial cells themselves, antibodies, complement, and both resident and infiltrating immune cells to be able to mount a timely response to a barrier breach and invasion by potentially pathogenic microbes. T cells fulfill a vital defensive role in the epithelia, with non-recirculating tissue resident memory T cells providing rapid specific immune protection against the pathogens most commonly encountered in barrier tissues, supported by innate immune cells and circulating T cells that can be called upon as needed [2, 3]. One trade-off of having a battalion of heavily armed T cells within the tissues is that loss of control or dysregulation of these cells can initiate and sustain chronic autoimmune and inflammatory diseases, such as Crohn’s disease, multiple sclerosis and psoriasis. Over the last decade, the contribution of Th17 cells has been recognized as a vital aspect of immunity at epithelial barriers [4]; however, Th17 cells and IL-17A have also been implicated in a number of their pathologies [5].IL-17A is a potent inducer of antimicrobial protein and peptide expression by epithelia. In the skin, IL-17A works synergistically with several cytokines including IFN-γ [6] and TNF-α [7] to potently drive the induction of a range of antimicrobial peptides and proteins including S100A7, A8 and A9, the cathelicidin LL-37 and human β-defensins (HBD)-2, 3 and 4. Working in concert, these antimicrobial peptides provide a broad spectrum of antibacterial activity and have also been demonstrated to have efficacy against some viruses [8]. In addition to their antimicrobial activities, the defensins have roles in the regulation of both innate and acquired immunity. HBD-2, 3 and 4 induce pro-inflammatory cytokine expression (IL-6, CXCL10, CCL2, CCL5 and CCL20), and the migration and proliferation of keratinocytes, promoting wound healing [9]. HBD-2 is also a chemoattractant for macrophages, mast cells, activated neutrophils, memory T cells and dendritic cells (DCs)[10]. The converse is also true: when used at a high enough concentration, chemokines like CCL20 have been shown to possess antimicrobial activities [11].
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影响因子：
56.9
作者：
D. Yang;O. Chertov;S. N. Bykovskaia;Q. Chen;M. J. Buffo;J. Shogan;M. Anderson;J. M. Schröder-J.-M.-S
通讯作者：
D. Yang;O. Chertov;S. N. Bykovskaia;Q. Chen;M. J. Buffo;J. Shogan;M. Anderson;J. M. Schröder-J.-M.-S
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16.8
作者：
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影响因子：
17.1
作者：
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影响因子：
3.8
作者：
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通讯作者：
Johnston, Andrew