Role of Central Leptin Signaling in the Starvation-Induced Alteration of B-Cell Development
Role of Central Leptin Signaling in the Starvation-Induced Alteration of B-Cell Development
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DOI：
10.1523/jneurosci.6562-10.2011
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发表时间：
2011-06
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通讯作者：
Miyako Tanaka;T. Suganami;Misa Kim-Saijo;C. Toda;M. Tsuiji;Kozue Ochi;Yasutomi Kamei;Y. Minokoshi-Y.-Minokos
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作者：
Miyako Tanaka;T. Suganami;Misa Kim-Saijo;C. Toda;M. Tsuiji;Kozue Ochi;Yasutomi Kamei;Y. Minokoshi-Y.-Minokos
营养缺乏或营养不良会抑制人和动物的免疫功能，从而增加对传染病的易感性。事实上，营养缺乏会导致胸腺和脾等淋巴组织萎缩，并减少循环中淋巴细胞的数量。瘦素是一种主要的脂肪细胞因子，仅在脂肪组织中产生，对营养状态做出反应，并作用于下丘脑，从而调节能量平衡。虽然瘦素在饥饿诱导的T细胞介导的免疫抑制中起着关键作用，但对其在饥饿条件下B细胞稳态中的作用却知之甚少。在这里，我们显示了禁食小鼠骨髓中B细胞发育的变化，其特征是前B细胞、前B细胞和未成熟B细胞减少，成熟B细胞增加。有趣的是，脑室注射瘦素足以防止禁食小鼠B细胞发育的改变。口服糖皮质激素受体拮抗剂RU486(11β-[p-(dimethylamino)phenyl]-17β-hydroxy-17-(1-propynyl)estra-4，9-dien-3-one).可明显防止禁食小鼠骨髓B系细胞的改变脑室注射神经肽Y Y1受体拮抗剂BIBP3226[(2R)-5-(diaminomethylideneamino)-2-[(2，2-diphenylacetyl)amino]-N-[(4-hydroxyphenyl)methyl]pentanamide]，和抑制升高的血清皮质酮浓度也能有效地预防这种情况。这项研究首次提供了体内证据，证明中枢瘦素信号在饥饿诱导的B细胞发育改变中所起的作用。这项研究的数据表明，整合整个生物体信息所固有的中枢神经系统能够控制免疫功能。
Nutritional deprivation or malnutrition suppresses immune function in humans and animals, thereby conferring higher susceptibility to infectious diseases. Indeed, nutritional deprivation induces atrophy of lymphoid tissues such as thymus and spleen and decreases the number of circulating lymphocytes. Leptin, a major adipocytokine, is exclusively produced in the adipose tissue in response to the nutritional status and acts on the hypothalamus, thereby regulating energy homeostasis. Although leptin plays a critical role in the starvation-induced T-cell-mediated immunosuppression, little is known about its role in B-cell homeostasis under starvation conditions. Here we show the alteration of B-cell development in the bone marrow of fasted mice, characterized by decrease in pro-B, pre-B, and immature B cells and increase in mature B cells. Interestingly, intracerebroventricular leptin injection was sufficient to prevent the alteration of B-cell development of fasted mice. The alteration of B lineage cells in the bone marrow of fasted mice was markedly prevented by oral administration of glucocorticoid receptor antagonist RU486 (11β-[p-(dimethylamino)phenyl]-17β-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one). It was also effectively prevented by intracerebroventricular injection of neuropeptide Y Y1 receptor antagonist BIBP3226 [(2R)-5-(diaminomethylideneamino)-2-[(2,2-diphenylacetyl)amino]-N-[(4-hydroxyphenyl)methyl]pentanamide], along with suppression of the otherwise increased serum corticosterone concentrations. This study provides the first in vivo evidence for the role of central leptin signaling in the starvation-induced alteration of B-cell development. The data of this study suggest that the CNS, which is inherent to integrate information from throughout the organism, is able to control immune function.