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A Basophil-Fibroblast Pro-inflammatory Axis Fuels Type 2 Skin Inflammation [RNA-Seq]

ABSTRACT: To better understand the contribution of basophils and fibroblast IL-4 signaling on type 2 skin inflammation, we conducted bulk-RNA seq on from normal and MC903 treated Isotype Cntrl + Mar1 and Il4rafl/fl + Il4raΔPdgfra models respectively.

ORGANISM(S): Mus musculus

PROVIDER: GSE288163 | GEO | 2025/08/04

REPOSITORIES: GEO

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A Basophil-Fibroblast Pro-inflammatory Axis Fuels Type 2 Skin Inflammation [scRNA-Seq]

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Project description:In this study, we explored gene expression profiles of CD34-CLEC12Ahi pre-basophils isolated from the bone marrow as well as CD34-CLEC12Alo mature basophils from the bone marrow and CD34+ basophil progenitors. We revealed that the gene expression of mature basophils isolated from the bone marrow and spleen resembled each other whereas pre-basophils and mature basophils showed distinct gene expression profiles.

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TLR-mediated basophil production of IL-4 and IL-13 in human and mouse

Project description:It has been previously shown that airway exposure to Toll-like receptor ligands through lipopolysaccharide (LPS)-contaminated house dust or bacterial infections can exacerbate allergic inflammation; however, the underlying mechanism(s) controlling this response have not been fully elucidated. Here we report that basophils are the major source of Th2 cytokines that respond to TLR4 ligands, such as LPS and lipid A, in human PBMC and murine spleen cells. LPS activated human PBMCs to up-regulate mRNAs for not only pro-inflammatory cytokines such as IL-6 and chemokines such as CXCL8 (IL-8), CCL2 (MCP-1), but also Th2 cytokines such as IL-4 and IL13. Among PBMCs, we identified CD123+/BDCA4- basophils as the major source of IL-4 and IL-13 in response to LPS. Even in the absence of IgE, purified human basophils, as well as a basophilic cell line, were directly activated by LPS to produce IL-4 and IL-13. Moreover, LPS-stimulated IL-4 knockin mouse (4get mice) spleens identified the basophils as the major IL-4 producing cells in a TLR4-dependent manner. These results indicate that bacterial LPS may play a role in type-2 immunity through direct activation of basophils to produce IL-4 and IL-13. Keywords: Cell type comparison

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