免疫学
下调和上调
粘膜免疫学
信号转导
细胞生物学
免疫球蛋白A
生物
抗体
免疫
基因
免疫系统
遗传学
免疫球蛋白G
作者
Kyle Kroll,Brady Hueber,Harikrishnan Balachandran,Nehal A. Afifi,Cordelia Manickam,Danielle Nettere,Justin Pollara,Andrew M. Hudson,Griffin Woolley,Lishomwa C. Ndhlovu,R. Keith Reeves
标识
DOI:10.1016/j.mucimm.2024.04.003
摘要
Immunoglobulin A (IgA) is the predominant mucosal antibody class with both anti- and pro-inflammatory roles [1-3]. However, the specific role of the IgA receptor CD89, expressed by a subset of natural killer (NK) cells, is poorly explored. We found that CD89 protein expression on circulating NK cells is infrequent in humans and rhesus macaques, but transcriptomic analysis showed ubiquitous CD89 expression, suggesting an inducible phenotype. Interestingly, CD89+ NK cells were more frequent in cord blood and mucosae, indicating a putative IgA-mediated NK cell function in the mucosae and infant immune system. CD89+ NK cells signaled through upregulated CD3ζ, SYK, ZAP70, and SLAMF1, but also showed high expression of inhibitory receptors such as KLRG1 and reduced activating NKp46 and NKp30. CD89-based activation or ADCC with monomeric IgA1 reduced NK cell functions, while ADCC with combinations of IgG and IgA2 was enhanced compared to IgG alone. These data suggest that functional CD89+ NK cells survey mucosal sites, but CD89 likely serves as regulatory receptor which can be further modulated depending on IgA and IgG subclass. Although the full functional niche of CD89+ NK cells remains unexplored, these intriguing data suggest the CD89 axis could represent a novel immunotherapeutic target in the mucosae or early life.
科研通智能强力驱动
Strongly Powered by AbleSci AI