Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian 116023, China.
Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian 116023, China.
J Immunol. 2019 Oct 1;203(7):1845-1856. doi: 10.4049/jimmunol.1900238. Epub 2019 Sep 4.
The immune signaling pathway mediated by Dectin-1 is important in mammals to modulate the production of IL-17 and TNF-α. Recently, IL-17 and TNF have also been characterized in invertebrates to play crucial roles in antibacterial immune responses, although the immune recognition and regulation mechanisms to produce IL-17 and TNF are still not well investigated. In the current study, a novel C-type lectin receptor (named CLec-HTM) with a signal peptide, a carbohydrate recognition domain, a transmembrane domain, and a nonclassical ITAM (hemITAM) in the cytoplasmic tail was identified from oyster CLec-HTM could bind LPS and various bacteria. After binding to its ligands, CLec-HTM was associated with the Src homology 2 (SH2) domain of spleen tyrosine kinase (Syk) by the hemITAM in its cytoplasmic tail to promote ERK (ERK) phosphorylation. The activated ERK could interact with Rel to induce Rel nuclear translocation. The Rel in the nucleus eventually induced the transcription of IL-17s and TNF. The results demonstrated that CLec-HTM with a broad binding spectrum of bacteria could be associated with Syk to transfer immune signals into the intracellular ERK-Rel pathway to induce IL-17 and TNF production.
Dectin-1 介导的免疫信号通路在哺乳动物中对于调节白细胞介素-17（IL-17）和肿瘤坏死因子-α（TNF-α）的产生非常重要。最近，IL-17 和 TNF 也在无脊椎动物中被表征为在抗菌免疫反应中发挥关键作用，尽管产生 IL-17 和 TNF 的免疫识别和调节机制仍未得到很好的研究。在本研究中，从牡蛎中鉴定出一种新型 C 型凝集素受体（命名为 CLec-HTM），其带有信号肽、碳水化合物识别结构域、跨膜结构域和细胞质尾部的非经典 ITAM（hemITAM）。CLec-HTM 可以结合 LPS 和各种细菌。在与配体结合后，CLec-HTM 通过其细胞质尾部的 hemITAM 与脾酪氨酸激酶（Syk）的 Src 同源 2（SH2）结构域结合，以促进 ERK（ERK）磷酸化。激活的 ERK 可以与 Rel 相互作用诱导 Rel 核转位。核内的 Rel 最终诱导 IL-17s 和 TNF 的转录。结果表明，具有广谱结合细菌能力的 CLec-HTM 可以与 Syk 结合，将免疫信号传递到细胞内的 ERK-Rel 途径，从而诱导 IL-17 和 TNF 的产生。
