Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network.

Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network.
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Langerhans细胞(LC)增殖介导了新生儿发育,体内平衡和与表皮LC网络的炎症相关扩张。

DOI:
10.1084/jem.20091586
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发表时间:
2009-12-21
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Geissmann F
Geissmann F
中科院分区:
其他
文献类型:
--
作者:
Chorro L;Sarde A;Li M;Woollard KJ;Chambon P;Malissen B;Kissenpfennig A;Barbaroux JB;Groves R;Geissmann F

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大多数组织由干细胞和前体细胞发育而来,随着其增殖潜能降低,这些细胞会发生分化。成熟的分化细胞很少增殖,在其生命末期会被源自前体细胞的新细胞所取代。表皮的朗格汉斯细胞(LCs)虽然起源于髓系,但已表明其在组织中的更新不依赖于骨髓,这提示存在真皮或表皮祖细胞。我们研究了参与朗格汉斯细胞发育和内稳态的机制。我们观察到,在小鼠胚胎第18天左右,一波朗格汉斯细胞前体被募集到表皮,并在出生后立即获得树突状形态、主要组织相容性复合体II、CD11c以及朗格汉斯蛋白的表达。然后,朗格汉斯蛋白阳性细胞在出生后第2天(P2)到第7天之间会经历一次大量的增殖爆发,其数量会增加10 - 20倍。在出生后的第一周之后,我们观察到表皮内朗格汉斯蛋白阳性细胞的低水平增殖。然而,在特应性皮炎(AD)小鼠模型中,一种角质形成细胞信号引发了表皮朗格汉斯细胞增殖增加。在人类特应性皮炎患者的表皮中也观察到了类似的结果。因此,分化的驻留细胞的增殖代表了某些髓系细胞群(如朗格汉斯细胞)在新生儿发育、内稳态以及成人中的一种替代途径。这种机制在白细胞迁移受限的部位可能具有相关性。
Most tissues develop from stem cells and precursors that undergo differentiation as their proliferative potential decreases. Mature differentiated cells rarely proliferate and are replaced at the end of their life by new cells derived from precursors. Langerhans cells (LCs) of the epidermis, although of myeloid origin, were shown to renew in tissues independently from the bone marrow, suggesting the existence of a dermal or epidermal progenitor. We investigated the mechanisms involved in LC development and homeostasis. We observed that a single wave of LC precursors was recruited in the epidermis of mice around embryonic day 18 and acquired a dendritic morphology, major histocompatibility complex II, CD11c, and langerin expression immediately after birth. Langerin+ cells then undergo a massive burst of proliferation between postnatal day 2 (P2) and P7, expanding their numbers by 10–20-fold. After the first week of life, we observed low-level proliferation of langerin+ cells within the epidermis. However, in a mouse model of atopic dermatitis (AD), a keratinocyte signal triggered increased epidermal LC proliferation. Similar findings were observed in epidermis from human patients with AD. Therefore, proliferation of differentiated resident cells represents an alternative pathway for development in the newborn, homeostasis, and expansion in adults of selected myeloid cell populations such as LCs. This mechanism may be relevant in locations where leukocyte trafficking is limited.
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