Cutting Edge: ATP13A2 Is an Endolysosomal Regulator of TLR9/7 Activation in Human Plasmacytoid Dendritic Cells.

IF 3.6 3区医学 Q2 IMMUNOLOGY

Journal of immunology Pub Date : 2024-07-15 DOI:10.4049/jimmunol.2300733

Purbita Bandopadhyay, Jafar Sarif, Ranit D'Rozario, Chinky Shiu Chen Liu, Bishnu P Sinha, Md Asmaul Hoque, Koustav Chatterjee, Supriyo Choudhury, Hrishikesh Kumar, Deblina Raychaudhuri, Dipyaman Ganguly

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引用次数: 0

Abstract

ATPase cation transporting 13A2 (ATP13A2) is an endolysosomal P-type ATPase known to be a polyamine transporter, explored mostly in neurons. As endolysosomal functions are also crucial in innate immune cells, we aimed to explore the potential role of ATP13A2 in the human immunocellular compartment. We found that human plasmacytoid dendritic cells (pDCs), the professional type I IFN-producing immune cells, especially have a prominent enrichment of ATP13A2 expression in endolysosomal compartments. ATP13A2 knockdown in human pDCs interferes with cytokine induction in response to TLR9/7 activation in response to bona fide ligands. ATP13A2 plays this crucial role in TLR9/7 activation in human pDCs by regulating endolysosomal pH and mitochondrial reactive oxygen generation. This (to our knowledge) hitherto unknown regulatory mechanism in pDCs involving ATP13A2 opens up a new avenue of research, given the crucial role of pDC-derived type I IFNs in protective immunity against infections as well as in the immunopathogenesis of myriad contexts of autoreactive inflammation.

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前沿：ATP13A2 是人类浆细胞树突状细胞中 TLR9/7 激活的溶酶体内调节器。

阳离子转运 ATPase 13A2（ATP13A2）是一种已知为多胺转运体的内溶酶体 P 型 ATPase，主要在神经元中进行研究。由于内溶酶体功能在先天性免疫细胞中也至关重要，因此我们旨在探索 ATP13A2 在人类免疫细胞区室中的潜在作用。我们发现，人类浆细胞树突状细胞（pDCs）是产生 I 型 IFN 的专业免疫细胞，其 ATP13A2 在内溶酶体区室中的表达尤其丰富。人类 pDCs 中的 ATP13A2 基因敲除会干扰 TLR9/7 激活后对真正配体的细胞因子诱导。ATP13A2 通过调节内溶酶体 pH 值和线粒体活性氧的生成，在人 pDC 的 TLR9/7 激活过程中发挥了关键作用。鉴于 pDC 衍生的 I 型 IFNs 在抗感染的保护性免疫以及各种自反应性炎症的免疫发病机制中发挥着至关重要的作用，这种涉及 ATP13A2 的迄今未知的 pDC 调节机制开辟了一条新的研究途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of immunology 医学-免疫学

CiteScore

8.20

自引率

2.30%

发文量

495

审稿时长

1 months

期刊介绍： The JI publishes novel, peer-reviewed findings in all areas of experimental immunology, including innate and adaptive immunity, inflammation, host defense, clinical immunology, autoimmunity and more. Special sections include Cutting Edge articles, Brief Reviews and Pillars of Immunology. The JI is published by The American Association of Immunologists (AAI)