Mutidirectional neutrophil migration. Neutrophil reverse transmigration from the subendothelial space to the circulation occurs predominantly after ischemia/reperfusion injury. After LTB4-driven neutrophil recruitment (1), infiltrated neutrophils interact with endothelial cells via CD11b and release NE, which degrades the JAM-C (2), allowing their circulation back to the bloodstream (3). Reverse-transmigrated neutrophils exhibit a distinct phenotype characterize by ICAM-1^highCXCR1^low. During pathogen-driven inflammation, infiltrated neutrophils may also return to lymphoid organs (bone marrow or lymph node) through the circulation or the lymphatic system. Inside the lymph nodes, neutrophils display an activated phenotype (CD11B^high, CD62L^low, CXCR2^low) and express MHC (CH)-II and the costimulatory molecules CD80 and CD86, suggesting a newly acquired ability to present antigens (4). Furthermore, this subpopulation of neutrophils is able to modulate the adaptive immune response by promoting or repressing the T- and B-cell function in the lymph node (6). Neutrophils migrating toward the bone marrow induce CD8⁺ T cell–dependent antiviral responses (5).