关键词: Epithelial barrier Interferon-lambda receptor 1 Mucosa Rhesus macaque Skin

Mesh : Animals Macaca mulatta Mouth Mucosa / immunology virology Skin / virology immunology metabolism Simian Acquired Immunodeficiency Syndrome / immunology virology Simian Immunodeficiency Virus / immunology physiology Humans Amino Acid Sequence Receptors, Interferon / genetics metabolism Cloning, Molecular

来  源:   DOI:10.1016/j.dci.2024.105236

Abstract:
Interferon-lambda receptor 1 (IFNLR1) is the key to interferon-lambda\'s biological activities. Rhesus macaques (Macaca mulatta) are supposedly more suitable for translational studies on interferon lambda-associated human diseases, yet little is known about their IFNLR1 (mmuIFNLR1). In this study, we cloned the coding sequence of mmuIFNLR1, examined its variants, and determined the distribution of mmuIFNLR1 mRNA and immunoreactivity in the buccal mucosa and arm skin of normal and immunodeficiency virus (SHIV/SIV) infected rhesus macaques. It was found that mmuIFNLR1 has 93.1% amino acid sequence identity to that of humans; all the amino acid residues of mmuIFNLR1 signal peptide, transmembrane region, PxxLxF motif and those essential for ligand binding are identical to that of humans; 6 variants of mmuIFNLR1, including the ones corresponding to that of humans were detected; IFNLR1 immunoreactivity was localized in primarily the epithelia of buccal mucosa and arm skin; SHIV/SIV infection could affect the levels of mmuIFNLR1 mRNA and immunoreactivity. These data expanded our knowledge on mmuIFNLR1 and provided a scientific basis for rational use of rhesus macaques in studies of IFN-λ associated human diseases like AIDS. Future studies testing IFNLR1-targeting therapeutics in rhesus macaques were warranted.
摘要:
干扰素-λ受体1(IFNLR1)是干扰素-λ生物学活性的关键。恒河猴(Macacamulatta)被认为更适合于干扰素λ相关人类疾病的翻译研究,然而,对它们的IFNLR1(mmuIFNLR1)知之甚少。在这项研究中,我们克隆了mmuIFNLR1的编码序列,检查了其变体,并确定了mmuIFNLR1mRNA在正常和免疫缺陷病毒(SHIV/SIV)感染的恒河猴的颊粘膜和手臂皮肤中的分布和免疫反应性。发现mmuIFNLR1与人类具有93.1%的氨基酸序列同一性;mmuIFNLR1信号肽的所有氨基酸残基,跨膜区,PxxLxF基序和配体结合所必需的基序与人类相同;检测到mmuIFNLR1的6种变体,包括与人类相对应的变体;IFNLR1免疫反应性主要位于颊粘膜和手臂皮肤的上皮中;SHIV/SIV感染可能会影响mmuIFNLR1mRNA的水平和免疫反应性。这些数据扩展了我们对mmuIFNLR1的了解,并为在IFN-λ相关人类疾病如AIDS的研究中合理使用恒河猴提供了科学依据。在恒河猴中测试IFNLR1靶向疗法的未来研究是有必要的。
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