脂多糖影响鼠CD103 + DC分化，改变了肺DC群体的平衡。,European Journal of Immunology

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脂多糖影响鼠CD103 + DC分化，改变了肺DC群体的平衡。
European Journal of Immunology ( IF 4.5 ) Pub Date : 2019-02-12 , DOI: 10.1002/eji.201847910
Julyanne Brassard ₁ , Catherine Maheux ₁ , Anick Langlois ₁ , Emilie Bernatchez ₁ , David Marsolais ₁ , Nicolas Flamand ₁ , Marie-Renee Blanchet ₁

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常规DC是异质性种群，它们是先天性和适应性免疫系统的桥梁。肺DC群包括CD103 + XCR1 + DC1s和CD11b + DC2s；它们的各种组合功能涵盖维持稳态所需的整个免疫反应范围。在这里，我们报道体内暴露于LPS会导致肺中CD103 + XCR1 + DC的比例发生深刻变化。使用离体LPS和TNF刺激鼠肺和脾脏分离的DC，我们表明这部分是由于GM-CSF诱导的DC CD103表达的直接下调。此外，我们证明，LPS诱导的全身性炎症会改变DC前体的转录特征，从而降低分化为XCR1 + DC的能力。同样，我们报道了TNF阻止了成熟前DC表达CD103的能力。总体而言，我们的结果表明，暴露于LPS不仅会影响前DC分化为XCR1 + DC的能力，还会降低其表达CD103的能力。这导致肺中CD103 + XCR1 + DC的比例降低，有利于CD11b + DC，这可能在LPS暴露后体内稳态的破坏中起作用，并决定了对LPS的免疫反应的性质。

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Lipopolysaccharide impacts murine CD103+ DC differentiation, altering the lung DC population balance.

Conventional DCs are a heterogeneous population that bridge the innate and adaptive immune systems. The lung DC population comprises CD103+ XCR1+ DC1s and CD11b+ DC2s; their various combined functions cover the whole spectrum of immune responses needed to maintain homeostasis. Here, we report that in vivo exposure to LPS leads to profound alterations in the proportions of CD103+ XCR1+ DCs in the lung. Using ex vivo LPS and TNF stimulations of murine lung and spleen-isolated DCs, we show that this is partly due to a direct downregulation of the GM-CSF-induced DC CD103 expression. Furthermore, we demonstrate that LPS-induced systemic inflammation alters the transcriptional signature of DC precursors toward a lower capacity to differentiate into XCR1+ DCs. Also, we report that TNF prevents the capacity of pre-DCs to express CD103 upon maturation. Overall, our results indicate that exposure to LPS directly impacts the capacity of pre-DCs to differentiate into XCR1+ DCs, in addition to lowering their capacity to express CD103. This leads to decreased proportions of CD103+ XCR1+ DCs in the lung, favoring CD11b+ DCs, which likely plays a role in the break in homeostasis following LPS exposure, and in determining the nature of the immune response to LPS.

更新日期：2019-02-12

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