The role of CD69 in acute neutrophil‐mediated inflammation

Abstract

The leukocyte activation marker CD69 functions as a negative regulator of the immune response, both in NK‐dependent tumor rejection and in the inflammation associated with lymphocyte‐dependent collagen‐induced arthritis. In contrast, it has been reported that CD69‐deficient mice are refractory to the neutrophil‐dependent acute inflammatory response associated with anti‐type II collagen antibody‐induced arthritis (CAIA), suggesting a positive regulatory role for CD69 in neutrophil function during arthritis induction. To clarify this discrepancy, the CAIA response was independently analyzed in our CD69‐deficient mice. In these experiments, the inflammatory response was unaffected by CD69 deficiency. Additionally, the <jats:italic>in vivo</jats:italic> down‐regulation of CD69 expression by treatment of wild‐type mice with the anti‐CD69 mAb 2.2, which mimics the CD69‐deficient phenotype, did not affect the course of arthritis in this model. Moreover, down‐regulation of CD69 expression increased expression in arthritic joints of key inflammatory mediators, including IL‐1β, IL‐6 and the chemokine MCP‐1. Neutrophil accumulation in zymosan‐treated air pouches and in thioglycolate‐treated peritoneal cavities was also unaffected in CD69‐deficient mice. In addition, CD69 expression was absent in activated neutrophils. Taken together, these results rule out a significant stimulatory role for CD69 in acute inflammatory responses mediated by neutrophils.