Biology subjects

Miglani, D.

Publications and source records attributed to Miglani, D..

2 recordsLinked to original sources

bioRxiv2026

Megakaryocyte emperipolesis arms neutrophils via intracellular provisioning

Neutrophils are phenotypically heterogenous cells that mediate host defense and tissue homeostasis. Here, we identify emperipolesis - the evolutionarily conserved process by which neutrophils pass through megakaryocytes - as a phenotypically transformative route of egress from bone marrow. By intravital microscopy and 3-D histology, we show that the rapid form emperipolesis is markedly enhanced under inflammatory conditions. Neutrophils exit from megakaryocytes directly to the blood, acquiring exosomes enriched in proteins related to metabolism, migration, and immune function. This transfer induces a distinct neutrophil phenotype characterized by enhanced glycolysis, oxidative phosphorylation, cytokine release, and longevity. Correspondingly, emperipolesis-educated neutrophils display accelerated migration in vitro and in vivo. Disrupting emperipolesis does not alter circulating neutrophil abundance but impairs neutrophil infiltration into inflamed tissues, including Pseudomonas aeruginosa-infected lung. These findings establish emperipolesis as a mechanism by which megakaryocytes amplify neutrophil-mediated immunity.

immunology↗

bioRxiv2025

A GPVI-platelet-neutrophil-NET axis drives systemic sclerosis

Systemic sclerosis (SSc) is immune-mediate inflammatory disease characterized by progressive tissue fibrosis. We observed that circulating neutrophils from patients with diffuse SSc exhibit an activated phenotype, a finding echoed in blood and skin transcriptomes. Neutrophil depletion abrogated experimental SSc induced by cutaneous injection of hypochlorous acid (HOCl) or bleomycin (BLM), and adoptive transfer of HOCl and BLM neutrophils induced skin and lung fibrosis in healthy mice, establishing neutrophils as necessary and sufficient for fibrosis. We noted that SSc patients exhibited platelet activation, a phenotype that preceded neutrophil activation in mice, suggesting an upstream role. Indeed, platelet depletion abrogated neutrophil activation and tissue fibrosis, and exposure to HOCl or BLM platelets conferred upon wild-type neutrophils the capacity to induce skin and lung fibrosis via neutrophil extracellular traps (NETs). Genetic and therapeutic blockade of the platelet collagen receptor GPVI attenuated platelet and neutrophil activation, reduced circulating NETs, and protected animals from skin and lung fibrosis. These findings identify the GPVI-platelet-neutrophil-NET as a new source of therapeutic targets in SSc.

immunology↗