Natural killer cell-mediated contact dermatitis-like reaction induced by treatment with TLR3 ligand poly(I:C).
Natural killer cell-mediated contact dermatitis-like reaction induced by treatment with TLR3 ligand poly(I:C).
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TLR3 配体聚 (I:C) 治疗诱导自然杀伤细胞介导的接触性皮炎样反应。
DOI：
10.1111/cod.14380
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发表时间：
2023
影响因子：
5.5
通讯作者：
Szczepanik,Marian
中科院分区：
文献类型：
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作者：
Majewska-Szczepanik,Monika;Kowalczyk,Paulina;Askenase,PhilipW;Szczepanik,Marian
Poly（I：C）被内体Toll样受体3（TLR 3）识别，并激活细胞毒性CD 8（+）淋巴细胞和自然杀伤（NK）细胞。已经表明，病毒TLR 3激动剂诱导稳健且持久的T细胞介导的应答。此外，TLR 3调节接触性超敏反应。本研究旨在确定聚（I：C）注射是否可以诱导NK介导的半抗原反应性的mice.MethodsMice与聚（I：C）治疗，并通过评估耳肿胀和血清干扰素γ（IFN-γ）的产生来测量其对二硝基氟苯半抗原的反应。连续细胞转移和细胞分选被用来调查的反应机制，和多聚（I：C）激活的肝脏NK细胞的表型通过流式细胞仪analysis.ResultsThe结果表明，聚（I：C）的管理增加耳肿胀，血清IFN-γ水平和半抗原的免疫功能正常和T-和B-细胞缺陷的小鼠。只有肝脏poly（I：C）激活的DX 5（+）NK细胞能够将对半抗原的反应性转移到初始受体中。Poly（I：C）对肝脏NK细胞的诱导作用依赖于TLR 3/TRIF-和IFN-γ-，不依赖于IL-12-，不受MyD 88的调节。结论本研究为Poly（I：C）如何刺激NK细胞介导的半抗原反应性提供了新的见解，并提示肝脏NK细胞可能在病毒感染过程中调节对非致病因素的免疫应答。
IntroductionPoly(I:C) is recognised by endosomal Toll‐like receptor 3 (TLR3) and activates cytotoxic CD8(+) lymphocytes and natural killer (NK) cells. It has been shown that the viral TLR3 agonist induces robust and long‐lasting T‐cell‐mediated responses. In addition, TLR3 modulates the contact hypersensitivity reaction.ObjectiveThis study aimed to determine whether poly(I:C) injection can induce NK‐mediated hapten reactivity in mice.MethodsMice were treated with poly(I:C), and their response to dinitrofluorobenzene hapten was measured by assessing ear swelling and serum interferon gamma (IFN‐γ) production. Adoptive cell transfer and cell sorting were used to investigate the mechanism of the reaction, and the phenotype of poly(I:C)‐activated liver NK cells was determined by flow cytometry analysis.ResultsThe results showed that poly(I:C) administration increased ear swelling, serum IFN‐γ levels and the response to hapten in both immunocompetent and T‐ and B‐cell‐deficient mice. Only liver poly(I:C)‐activated DX5(+) NK cells were able to transfer reactivity to hapten into a naive recipient. Induction of liver NK cells after poly(I:C) administration was TLR3/TRIF‐ and IFN‐γ‐dependent, interleukin 12‐independent, and not modulated by MyD88.ConclusionThis study provides new insights into how poly(I:C) stimulates NK‐mediated reactivity to hapten and suggests that liver NK cells may modulate the immune response to non‐pathogenic factors during viral infection.