A Major Population of Functional KLRG1(-) ILC2s in Female Lungs Contributes to a Sex Bias in ILC2 Numbers.
A Major Population of Functional KLRG1(-) ILC2s in Female Lungs Contributes to a Sex Bias in ILC2 Numbers.
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DOI：
10.4049/immunohorizons.1800008
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发表时间：
2018-03
期刊：
影响因子：
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通讯作者：
Kovats S
中科院分区：
文献类型：
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作者：
Kadel S;Ainsua-Enrich E;Hatipoglu I;Turner S;Singh S;Khan S;Kovats S
人类在呼吸道疾病（包括哮喘和病毒感染）的发病率和严重程度方面存在显著的性别差异。在与呼吸系统疾病相关的2型炎症中，性激素导致女性性别偏见，这与最近的报道一致，即女性肺部含有更多数量的加塔-3依赖性第2组先天淋巴细胞（ILC 2）。在这项研究中，我们确定性激素水平是否支配小鼠肺和骨髓（BM）中ILC 2的数量、表型和功能的性别差异。我们的数据显示，雌性小鼠的肺在体内平衡中具有显著更大的ILC 2数量，部分原因是ILC 2的主要子集缺乏巨噬细胞凝集素样受体G1（KLRG 1），这是一个在雄性小鼠肺中基本上不存在的群体。KLRG 1 − ILC 2能够产生2型细胞因子，并且在性成熟后随着年龄的增长而增加，这表明女性中存在独特的功能子集。对性腺切除小鼠或具有整体或淋巴细胞限制性雌激素受体α（Esr 1）缺陷的小鼠进行的实验表明，雄激素而不是雌激素调节肺和BM中KLRG 1 − ILC 2亚群和ILC 2功能能力的数量，以及BM ILC 2中加塔-3表达的水平。此外，BM PLZF+ ILC前体的频率在雄性中更高，并且通过过量的雄激素增加，表明雄激素用于抑制ILC前体向ILC 2的转变。总之，这些数据表明，女性中KLRG 1 − ILC 2的功能亚群有助于在生育年龄后观察到的肺ILC 2的性别偏见。
Humans show significant sex differences in the incidence and severity of respiratory diseases, including asthma and virus infection. Sex hormones contribute to the female sex bias in type 2 inflammation associated with respiratory diseases, consistent with recent reports that female lungs harbor greater numbers of GATA-3–dependent group 2 innate lymphoid cells (ILC2s). In this study, we determined whether sex hormone levels govern sex differences in the numbers, phenotype, and function of ILC2s in the murine lung and bone marrow (BM). Our data show that lungs of female mice harbor significantly greater ILC2 numbers in homeostasis, in part due to a major subset of ILC2s lacking killer-cell lectin like receptor G1 (KLRG1), a population largely absent in male lungs. The KLRG1− ILC2s were capable of type 2 cytokine production and increased with age after sexual maturity, suggesting that a unique functional subset exists in females. Experiments with gonadectomized mice or mice bearing either global or lymphocyte restricted estrogen receptor α (Esr1) deficiency showed that androgens rather than estrogens regulated numbers of the KLRG1− ILC2 subset and ILC2 functional capacity in the lung and BM, as well as levels of GATA-3 expression in BM ILC2s. Furthermore, the frequency of BM PLZF+ ILC precursors was higher in males and increased by excess androgens, suggesting that androgens act to inhibit the transition of ILC precursors to ILC2s. Taken together, these data show that a functional subset of KLRG1− ILC2s in females contributes to the sex bias in lung ILC2s that is observed after reproductive age.