Crosstalk between neutrophils and hepatic stellate cells in liver injury and repair: Mechanisms and implications

doi:10.3748/wjg.121310

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World Journal of Gastroenterology

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1007-9327

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World J Gastroenterol. Nov 21, 2026; 32(43): 121310
Published online Nov 21, 2026. doi: 10.3748/wjg.121310

Table 1 Stage-specific operational framework for neutrophil-hepatic stellate cells crosstalk and therapeutic posture

Stage	Clinical/histological window	Dominant cellular-molecular signature	Neutrophil functional output	Therapeutic posture
I Acute injury (hours-days)	ALT/AST ↑↑, no fibrosis	Ly6G^hi infiltration peak; transient MPO-DNA/cit-H3↑; early αSMA induction	Dual: Early cytotoxic; late reparative	Selective: PAD4 inhibition + NLRP3 dampening in early window; preserve late reparative phenotype
II Chronic active fibrosis (months-years)	NLR ↑, FibroScan ≥ 8.5 kPa or ELF ≥ 9.8, F2-F3	Sustained MPO-DNA/cit-H3 ↑; CCL2, CXCL10 ↑; persistent NETs-HSCs loop	Self-amplifying pro-fibrotic	Disrupt loop: COX-2 + NLRP3 + TGFβR1; avoid prolonged NETs ablation
III Cirrhosis/HCC (F4⁺ tumor)	High NLR, PIVKA-II/AFP ↑	PD-L1⁺/PLAUR⁺ TANs; NETs-rich immune-excluded niche	Pro-tumor, immunosuppressive	Combination: PAD4 or NLRP3 + TGFβR1 + ICI; close infection monitoring

ALT: Alanine transaminase; AST: Aspartate aminotransferase; MPO: Myeloperoxidase; PAD4: Peptidylarginine deiminase 4; NLRP3: NOD-like receptor family pyrin domain containing 3; NLR: Neutrophil-to-lymphocyte ratio; NETs: Neutrophil extracellular traps; HSCs: Hepatic stellate cells; COX-2: Cyclooxygenase-2; HCC: Hepatocellular carcinoma; TGFβR1: Transforming growth factor-β receptor 1; ICI: Immune checkpoint inhibitor.

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Citation: Lian YJ, Li MY, Wang L, Gao YW, Zhu D, Lyu WL. Crosstalk between neutrophils and hepatic stellate cells in liver injury and repair: Mechanisms and implications. World J Gastroenterol 2026; 32(43): 121310
URL: https://www.wjgnet.com/1007-9327/full/v32/i43/121310.htm
DOI: https://dx.doi.org/10.3748/wjg.121310

Lian YJ, Li MY, Wang L, Gao YW, Zhu D, Lyu WL. Crosstalk between neutrophils and hepatic stellate cells in liver injury and repair: Mechanisms and implications. World J Gastroenterol 2026; 32(43): 121310 [DOI: 10.3748/wjg.121310]

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