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Gene Expression Analysis on Neutrophil-Dendritic Hybrid Cells in Synovial Fluid from Rheumatoid Arthritis (RA) Patient

Yun Liu, Toshio Ota, Xiaohuan Chen, Hallie Dolin, Karen Pan, Akira Takashima, Atsushi Hinohara and Zhixing K Pan

Neutrophils, as we have recently discovered, can differentiate into a unique leukocyte population expressing surface markers of both neutrophils and dendritic cells (DCs). The resulting population, termed "neutrophil-DC hybrid", retains the functionality of professional phagocytes while acquiring the properties of professional antigen presenting cells (APCs). In all tested mouse models of inflammatory diseases, hybrid cells emerged at inflammatory lesions, where they functioned as both phagocytes and APCs. Our central hypothesis is that neutrophil-DC hybrids play an important pathogenic role in a variety of inflammatory diseases, including rheumatoid arthritis (RA), psoriasis, and inflammatory bowel disease. If this is correct, one should then be able to treat these disorders by intercepting local transdifferentiation of neutrophils into the hybrids, blocking specific functions of the hybrid cells, or selectively killing the hybrid cells. As the first step in testing this concept, we are in the process of identifying unique genes that are expressed predominantly by the neutrophil-DC hybrids purified from synovial fluid samples from RA patients. We demonstrated that neutrophil-DC hybrids are present at the inflammatory lesions of RA patients. By using micro-array analysis, we investigated the gene expression profile of hybrids and the unique gene products expressed by neutrophil-DC hybrids in synovial fluid from rheumatoid arthritis patients. Our results demonstrated that transdifferentiation occurs in the joints of the RA patients, suggesting an expanded role for neutrophils in potential contribution to host adaptive immune processes.