Age-related changes in the local milieu of inflamed tissues cause aberrant neutrophil trafficking and subsequent remote organ damage

• DOI: 10.1016/j.immuni.2021.04.025
• Publication Date: 2021-05-24T14:28:31Z
• Authors: Anna Barkaway; Loïc Rolas; Régis Joulia; Jennifer Bodkin; Tchern Lenn; Charlotte Owen-Woods; Natalia Reglero-Real; Monja Stein; Laura Vázquez-Mar...; Tamara Girbl; Robin N. Poston; Matthew Golding; Rebecca S. Saleeb; Aude Thiriot; Ulrich H. von And...; Johan Duchene; Mathieu-Benoit Vo...; Cleo L. Bishop; David Voehringer; Axel Roers; Antal Rot; Tim Lämmermann; Sussan Nourshargh
• Keywords: CXCL1; CXC chemokine receptors; Intravital microscopy; CXCL2; Neutrophil Extracellular Traps

Aging is associated with dysregulated immune functions. Here, we investigated the impact of age on neutrophil diapedesis. Using confocal intravital microscopy, found that in aged mice, neutrophils adhered to vascular endothelium inflamed tissues but exhibited a high frequency reverse transendothelial migration (rTEM). This retrograde breaching by was governed enhanced production chemokine CXCL1 from mast cells localized at endothelial cell (EC) junctions. Increased EC expression atypical receptor 1 (ACKR1) supported this pro-inflammatory milieu venules. Accumulation caused desensitization CXCR2 and loss directional motility within Fluorescent tracking revealed undergoing rTEM re-entered circulation disseminated lungs where they leakage. Thus, stemming local inflammatory site contribute remote organ damage, implication systemic inflammation aging.