Williams Abigael P, Turner Sean, Chlebicz Magdalena, Carter Hannah, Miller Reegan A J, Allushi Bujana, Roe Mandi M, Mejia Laura Loriel, Labombarde Jocelyn, Alberola-Ila José, Kovats Susan
Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States.
Department of Microbiology & Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.
J Immunol. 2025 Aug 1;214(8):1891-1897. doi: 10.1093/jimmun/vkaf114.
Pulmonary type 2 innate lymphocytes (ILC2s) show sex dimorphism in numbers, phenotype, and function. We used a novel strategy of competitive, mixed male-female donor bone marrow chimeras to determine if sex differences in murine ILC2s result from extrinsic factors in the recipient environment or from durable intrinsic variables in donor cells. We show that the recipient sex environment regulated ILC2 numbers and IL33R/ST2 and KLRG1 surface levels, independent of donor sex. In contrast, ILC2 production of interleukin (IL)-5 depended on donor cell sex and the type of inflammatory stimulus. After allergen exposure, or upon treatment of naïve lung cells with PMA/ionomycin, a higher frequency of female donor-derived ILC2s produced IL-5. In contrast, influenza virus infection induced a greater proportion of male donor-derived ILC2s to produce IL-5. Thus, while a current sex environment governed pulmonary ILC2 numbers and canonical markers, ILC2 functional responses were shaped by durable factors stemming from intrinsic biological sex.
肺部2型固有淋巴细胞（ILC2s）在数量、表型和功能上表现出性别差异。我们采用了一种新型策略，构建具有竞争性的、雄性和雌性供体骨髓混合嵌合体，以确定小鼠ILC2s的性别差异是源于受体环境中的外在因素，还是供体细胞中持久的内在变量。我们发现，受体性别环境可调节ILC2数量以及IL33R/ST2和KLRG1的表面水平，且与供体性别无关。相比之下，ILC2产生白细胞介素（IL）-5的情况则取决于供体细胞的性别以及炎症刺激的类型。过敏原暴露后，或者用佛波酯/离子霉素处理未致敏的肺细胞后，来自雌性供体的ILC2s产生IL-5的频率更高。相比之下，流感病毒感染则诱导更多来自雄性供体的ILC2s产生IL-5。因此，虽然当前的性别环境决定了肺部ILC2的数量和典型标志物，但ILC2的功能反应却是由内在生物学性别产生的持久因素所塑造的。
