A two-step human culture system replicates intestinal monocyte maturation cascade: Conversion of tissue-like inflammatory monocytes into macrophages.,European Journal of Immunology

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A two-step human culture system replicates intestinal monocyte maturation cascade: Conversion of tissue-like inflammatory monocytes into macrophages.
European Journal of Immunology ( IF 4.5 ) Pub Date : 2020-06-19 , DOI: 10.1002/eji.202048555
Marwa Bsat ₁ , Laurence Chapuy ₁ , Manuel Rubio ₁ , Marika Sarfati ₁

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Monocyte maturation program into macrophages (MΦ) is well defined in murine gut under homeostatic or inflammatory conditions. Obviously, in vivo tracking of monocytes in inflamed tissues remains difficult in humans. Furthermore, in vitro models fall short in generating the surrogates of transient extravasated tissue inflammatory monocytes. Here, we aimed to unravel environmental cues that replicated the human monocyte “waterfall” process in vitro by first, generating tissue‐like inflammatory monocytes, which were then shifted toward MΦ. Purified CD14⁺CD16⁻ monocytes, cultured with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), IFN‐γ and IL23, differentiated into CD14⁺CD163⁻ cells that displayed a monocyte‐like morphology. In vitro generated inflammatory CD14⁺CD163⁻ (inflammatory monocyte‐like cells) cells promoted IL‐1β‐dependent memory Th17 and Th17/Th1 responses, like the CD14⁺CD163⁻ mo‐like cells that accumulate in inflamed colon of Crohn's disease patients. Next, in vitro generated inflammatory monocyte‐like cells converted to functional CD163⁺ MΦ following exposure to TGF‐β and IL10. Gene set enrichment analysis further revealed a shared molecular signature between converted CD163⁺ MΦ and MΦ detected in various inflamed nonlymphoid and lymphoid diseased tissues. Our findings propose a two‐step in vitro culture that recapitulates human monocyte maturation cascade in inflamed tissue. Manipulation of this process might open therapeutic avenues for chronic inflammatory disorders.

中文翻译：

两步人类培养系统复制了肠道单核细胞成熟级联反应：将组织样炎性单核细胞转化为巨噬细胞。

在稳态或炎性条件下，在鼠肠中将单核细胞成熟程序转变为巨噬细胞（MΦ）是很明确的。显然，在人类中，在体内很难追踪发炎组织中的单核细胞。此外，体外模型不足以产生瞬时外渗的组织炎性单核细胞的替代物。在这里，我们旨在揭示先在体外复制人类单核细胞“瀑布”过程的环境线索，产生组织样炎性单核细胞，然后将其转移至MΦ。纯化的CD14 ⁺ CD16 ^-单核细胞，用粒细胞巨噬细胞集落刺激因子（GM-CSF），IFN-γ和IL23，分化成CD14培养⁺ CD163 ^-表现出单核细胞样形态的细胞。体外产生的炎性CD14 ⁺ CD163 ^-（炎性单核细胞样细胞）的细胞促进IL-1β依赖性记忆的Th17和Th17 / Th1应答，如CD14 ⁺ CD163 ^-莫状，在克罗恩病患者的发炎的结肠积累细胞。接下来，在暴露于TGF-β和IL10后，体外产生的炎性单核细胞样细胞转化为功能性CD163 ⁺ MΦ。基因集富集分析进一步揭示了转化的CD163 ⁺之间的共享分子标记在各种发炎的非淋巴和淋巴病变组织中检测到MΦ和MΦ。我们的发现提出了两步体外培养，概述了发炎组织中人单核细胞成熟级联反应。操纵该过程可能为慢性炎性疾病开辟治疗途径。

更新日期：2020-06-19

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