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TNFR1 signaling in sympathetic nerves dampens the inflammatory response in the bone marrow

ABSTRACT: Hematological malignancies and cytotoxic therapy induce sympathetic neuropathy in the bone marrow (BM), leading to niche remodeling, disease progression, and impaired hematopoiesis regeneration after myeloablative therapy. Vincristine induces pro-inflammatory cytokine production in the BM, including tumor necrosis factor a (TNF-a), impairs hematopoietic stem cell function, and harms sympathetic neurons. Deleting TNF receptor R1 (TNFR1) in sympathetic nerves exacerbated hematopoietic stem cell exhaustion. Mechanistically, loss of sympathetic nerve-specific TNFR1 signaling prevented the increase of norepinephrine levels in the BM after vincristine treatment, leading to delayed inflammation resolution due to elevated IL-6 production by BM endothelial cells. Therefore, TNFR1 signaling in sympathetic nerves plays a role in the resolution of the inflammatory state after vincristine treatment. Therapeutic strategies meant to reduce inflammation should be considered to prevent long-term hematopoietic damage in cancer patients.

ORGANISM(S): Mus musculus

PROVIDER: GSE305591 | GEO | 2025/08/31

REPOSITORIES: GEO

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TNFR1 signaling in sympathetic nerves dampens the inflammatory response in the bone marrow

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