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Convergent evolution of MDP-monocyte differentiation in adult skin permits repair of the Langerhans cell network [RNA-seq]

ABSTRACT: Convergent evolution of MDP-monocyte differentiation in adult skin permits repair of the Langerhans cell network [RNA-seq]

PROVIDER: PRJNA1040849 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26842614_1.fastq.gz	Fastqsanger.gz
	SRR26842614_2.fastq.gz	Fastqsanger.gz
	SRR26842615_1.fastq.gz	Fastqsanger.gz
	SRR26842615_2.fastq.gz	Fastqsanger.gz
	SRR26842616_1.fastq.gz	Fastqsanger.gz

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Convergent evolution of MDP-monocyte differentiation in adult skin permits repair of the Langerhans cell network

Project description:Convergent evolution of MDP-monocyte differentiation in adult skin permits repair of the Langerhans cell network

| PRJNA1040853 | ENA

Convergent evolution of MDP-monocyte differentiation in adult skin permits repair of the Langerhans cell network [scRNA-seq]

Project description:Convergent evolution of MDP-monocyte differentiation in adult skin permits repair of the Langerhans cell network [scRNA-seq]

| PRJNA1040858 | ENA

Convergent evolution of MDP-monocyte differentiation in adult skin permits repair of the Langerhans cell network [RNA-seq]

Project description:Langerhans cells (LCs) are a unique population of phagocytes programmed within embryonic skin to maintain tissue and immunological homeostasis at the epidermal barrier site. Unique amongst tissue-resident macrophages, LCs play roles in skin innervation and repair, while also functioning as migrating professional antigen presenting cells, a capability classically assigned to dendritic cells (DC). We current lack insight into the molecular pathways that determine this dichotomy, when they are established, and whether precursors recruited to the adult skin niche access the same instructive signals laid down in utero. Tracking differentiation of monocyte-derived (m)LCs after destruction of embryo-derived cells in murine adult skin, revealed intrinsic intra-epidermal heterogeneity and selection of MDP-monocytes to by-pass gene programmes specifying a macrophage fate. Adopting a process unique to adult skin, subsequent extrinsic specification of EpCAM+ precursors via follicular Notch ligands, and aryl hydrocarbon receptor (Ahr) signalling, combined to determine commitment to resident mLCs. Using a unique human LC dataset, we demonstrated that embryo-derived (e)LCs in newborn human skin retained transcriptional evidence of their macrophage origin, which was superseded by a distinct DC-like immune modules following proliferation in infant skin. Thus, convergent differentiation of monocytes within adult skin exploits novel molecular pathways to replicate conditioning of eLC towards more immunogenic DC-like cells within post-natal skin.

2024-09-08 | GSE247874 | GEO

Convergent evolution of MDP-monocyte differentiation in adult skin permits repair of the Langerhans cell network [scRNA-seq]

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Convergent evolution of monocyte differentiation in adult skin instructs Langerhans cell identity

Project description:Convergent evolution of monocyte differentiation in adult skin instructs Langerhans cell identity

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Convergent evolution of MDP-monocyte differentiation in adult skin permits repair of the Langerhans cell network

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-09-08 | GSE247879 | GEO

Convergent evolution of monocyte differentiation in adult skin instructs Langerhans cell identity

Project description:Langerhans cells (LCs) maintain tissue and immunological homeostasis at the epidermal barrier site. They are unique among phagocytes in functioning both as embryo-derived, tissue-resident macrophages that influence skin innervation and repair, and as migrating professional antigen presenting cells, a capability classically assigned to dendritic cells (DC). Here we report the mechanisms that determine this dual identity. Using ablation of embryo-derived LCs in murine adult skin and tracked differentiation of incoming monocyte-derived replacements, we reveal intrinsic intra-epidermal heterogeneity. Macrophage-dendritic cell precursors are selected for survival in the skin environment, by-passing gene programs that specify a macrophage fate. We demonstrate that the hair follicle niche provides Notch signals that impose LC identity. In human skin, we show that embryo-derived (e)LCs in newborns retain transcriptional evidence of their macrophage origin, but this is superseded by distinct DC-like immune modules after expansion of the eLC network. Thus, cellular adaptation to the adult skin niche replicates conditioning of eLC, instructing DC-like programmes within macrophages

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Trancriptomics of primary human monocytes, Langerhans cells (LC), and monocyte-derived Langerhans cells (moLC)

Project description:Trancriptomics of primary human monocytes, Langerhans cells (LC), and monocyte-derived Langerhans cells (moLC)

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Serotonin 2A Receptor Attenuates Psoriatic Inflammation by Suppressing IL-23 Secretion in Monocyte-derived Langerhans cells

Project description:Serotonin and its receptor are known to play a role in regulating immune cells. However, how they affect an autoimmune disease like psoriasis is not well-established and the mechanism remains to be elucidated. Here, we investigated the role played by serotonin 2A receptor (HTR2A) in regulating psoriasis. HTR2A antagonistic drug worsens psoriatic outcome and HTR2A modulation reduced psoriatic inflammation. Using Imiquimod-induced psoriasiform inflammation model, HTR2A-deficient mice experienced exacerbated inflammation. Hematopoietic cells, particularly monocyte-derived Langerhans cells, were responsible for this exacerbated inflammation. Mechanistically, the exacerbated inflammation is due to increased interleukin-23 (IL-23) secretion and HTR2A suppresses it by inhibiting the activation of non-canonical NFkB pathway. Platelet-derived serotonin is the putative agonist modulating HTR2A attenuating psoriatic inflammation. Lastly, our findings in mice were also reproduced clinically. Thus, our data demonstrate platelet serotonin putatively modulates HTR2A attenuating psoriatic inflammation by suppressing IL-23 secretion via inhibiting non-canonical NFkB pathway in monocyte-derived Langerhans cells.

2025-07-23 | GSE274449 | GEO

Serotonin 2A Receptor Attenuates Psoriatic Inflammation by Suppressing IL-23 Secretion in Monocyte-derived Langerhans cells (mouse)

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