The MRGPRX2-Substance P pathway regulates mast cell migration

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES iScience Pub Date : 2024-09-16 DOI:10.1016/j.isci.2024.110984

Peter W. West, Jérémy Chéret, Rajia Bahri, Orsolya Kiss, Zining Wu, Colin H. Macphee, Silvia Bulfone-Paus

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Abstract

Mast cells (MC) are tissue-resident immune cells known to degranulate in response to FcεRI crosslinking or MRGPRX2 engagement. MCs are found close to nerves, but the mechanisms that regulate this privileged localization remain unclear. Here, we investigated MRGPRX2 expression patterns and specific activities in MCs. We show that MRGPRX2 expression is heterogeneous in human MC progenitors and mature MCs. Substance P (SP) is a rapid and specific activator of MRGPRX2, and long-term supplementation of MCs with SP expands MRGPRX2-expressing cells.

While high concentrations of SP induce rapid MC degranulation, low concentrations prompt immature MC chemotaxis. Lastly, we demonstrate that in inflammatory skin conditions like psoriasis, the number of MRGPRX2⁺ MCs is increased, and during in vitro skin re-innervation, MRGPRX2⁺ MCs preferentially reside in proximity to and migrate towards SP⁺ nerve fibres. This indicates that SP-MRGPRX2 signalling defines MC positioning and relocation within tissues and promotes immune cell-nerve fibre communication.

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MRGPRX2-Substance P 通路调控肥大细胞迁移

众所周知，肥大细胞（MC）是一种组织驻留免疫细胞，会因 FcεRI 交联或 MRGPRX2 的参与而脱颗粒。肥大细胞靠近神经，但调节这种特异性定位的机制仍不清楚。在这里，我们研究了 MCs 中 MRGPRX2 的表达模式和特异性活性。我们发现，MRGPRX2 在人类 MC 祖细胞和成熟 MC 中的表达具有异质性。物质 P（SP）是 MRGPRX2 快速而特异的激活剂，长期给 MCs 补充 SP 会扩大 MRGPRX2 表达的细胞。最后，我们证明，在银屑病等皮肤炎症中，MRGPRX2+ MCs 的数量会增加，在体外皮肤神经再支配过程中，MRGPRX2+ MCs 会优先驻留在 SP+ 神经纤维附近并向其迁移。这表明，SP-MRGPRX2 信号确定了 MC 在组织内的定位和迁移，并促进了免疫细胞与神经纤维之间的交流。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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