Wnt/β-catenin和NF-κB信号串扰在褪黑激素核受体介导单色光影响鸡淋巴细胞增殖中的作用

褪黑激素是外界光照刺激同体内细胞响应协调关系中的重要信号，特点是同时拥有膜受体和核受体。我们前一结题基金研究发现单色绿光能刺激雏鸡褪黑激素分泌，经膜受体介导淋巴细胞增殖，提高免疫功能。新近发现褪黑激素核受体3个亚型对调控细胞存活、增殖和分化起重要又不同的作用，但褪黑激素核受体在单色光诱导鸡淋巴细胞增殖中的作用机制仍不完全清楚。本课题利用体内与体外试验探究单光色影响鸡不同免疫器官褪黑激素核受体亚型表达的差异，褪黑激素在调控单色光诱导鸡T、B淋巴细胞增殖中核受体是何发挥作用、如何发挥作用（核受体亚型途径）、怎样发挥作用（胞内信号途径和Wnt/β-catenin与NF-κB信号串扰作用）。从细胞与分子水平进一步阐明单色光诱导鸡淋巴细胞增殖的机制：褪黑激素作用假说，有助于揭示环境因子（光色）影响机体功能基因表达的内在联系，为合理利用光色提高家禽免疫力和克服大量使用抗生素的负面影响提供新的突破点。

Melatonin is a critical signaling for rapport between environmental light information and cellular response to the body, and its characteristic contains both membrane receptor and nuclear receptor. Our previous studies have shown that monochromatic green light stimulated melatonin secretion to induce lymphocyte proliferation and to promote immune function in the chicks via melatonin membrane receptor pathway. However, the melatonin nuclear receptors are consisted of three subtypes, and play the various functions for controlling call survival, proliferation and differentiation, but how melatonin nuclear receptors mediate the monochromatic light-induced lymphocyte proliferation still remains unclear. Both studies of in vivo and in vitro were used in this study to expose (1) the role of monochromatic light in differential expression of melatonin nuclear receptor in various immune organs, (2) whether effect of melatonin nuclear receptor on the monochromatic light-induced lymphocyte proliferation, (3) mechanisms whereby melatonin nuclear receptor mediates monochromatic light-induced lymphocyte proliferation, and (4) mechanisms underlying how physiological crosstalk between Wnt/β-catenin and NF-κB intracellular signaling pathways on melatonin modulates monochromatic light-induced lymphocyte proliferation. These studies will clarify the hypothesis by which melatonin modulates monochromatic light-induced lymphocyte proliferation in the chickens at the cellular and molecular levels. This study will be helpful to discover the inner relationship between the environment factor (such as light spectra) and the avian functional gene expression, and to provide a new theoretical guidance in improving the avian immune function and helping to deal with the problem of antibiotic abuse by using new light spectra.