鉴定出自身免疫病位点Bphs为组胺受体H1。

Identification of Bphs, an autoimmune disease locus, as histamine receptor H1.

作者信息

Ma Runlin Z, Gao Jianfeng, Meeker Nathan D, Fillmore Parley D, Tung Kenneth S K, Watanabe Takeshi, Zachary James F, Offner Halina, Blankenhorn Elizabeth P, Teuscher Cory

机构信息

Laboratory Animal Center, Institute of Genetics, Chinese Academy of Sciences, Beijing, China 100101.

出版信息

Science. 2002 Jul 26;297(5581):620-3. doi: 10.1126/science.1072810.

DOI:10.1126/science.1072810

PMID:12142541

Abstract

Bphs controls Bordetella pertussis toxin (PTX)-induced vasoactive amine sensitization elicited by histamine (VAASH) and has an established role in autoimmunity. We report that congenic mapping links Bphs to the histamine H1 receptor gene (Hrh1/H1R) and that H1R differs at three amino acid residues in VAASH-susceptible and -resistant mice. Hrh1-/- mice are protected from VAASH, which can be restored by genetic complementation with a susceptible Bphs/Hrh1 allele, and experimental allergic encephalomyelitis and autoimmune orchitis due to immune deviation. Thus, natural alleles of Hrh1 control both the autoimmune T cell and vascular responses regulated by histamine after PTX sensitization.

摘要

Bphs可控制百日咳博德特氏菌毒素（PTX）诱导的由组胺引发的血管活性胺致敏作用（VAASH），并在自身免疫中发挥既定作用。我们报告称，同源基因定位将Bphs与组胺H1受体基因（Hrh1/H1R）联系起来，并且在对VAASH敏感和抗性的小鼠中，H1R在三个氨基酸残基处存在差异。Hrh1基因敲除小鼠对VAASH具有抗性，通过与易感的Bphs/Hrh1等位基因进行基因互补可恢复该敏感性，同时还可预防实验性变应性脑脊髓炎和因免疫偏差导致的自身免疫性睾丸炎。因此，Hrh1的天然等位基因可控制PTX致敏后由组胺调节的自身免疫性T细胞和血管反应。