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Cutting Edge: Novel Human Dendritic Cell- and Monocyte-Attracting Chemokine-Like Protein Identified by Fold Recognition Methods

M. Teresa Pisabarro^1,*,||, Beatrice Leung, Mandy Kwong, Racquel Corpuz, Gretchen D. Frantz, Nancy Chiang^¶, Richard Vandlen, Lauri J. Diehl, Nicholas Skelton^*, Hok Seon Kim^¶, Dan Eaton and Kerstin N. Schmidt^1,

^* Department of Protein Engineering, Department of Immunology, Department of Protein Chemistry, Department of Pathology, and ^¶ Department of Antibody Engineering, Genentech Inc., South San Francisco, CA 94080; and ^|| Department of Bioinformatics, BIOTEC TU, Dresden, Germany

Chemokines play an important role in the immune system by regulating cell trafficking in homeostasis and inflammation. In this study, we report the identification and characterization of a novel cytokine-like protein, DMC (dendritic cell and monocyte chemokine-like protein), which attracts dendritic cells and monocytes. The key to the identification of this putative new chemokine was the application of threading techniques to its uncharacterized sequence. Based on our studies, DMC is predicted to have an IL-8-like chemokine fold and to be structurally and functionally related to CXCL8 and CXCL14. Consistent with our predictions, DMC induces migration of monocytes and immature dendritic cells. Expression studies show that DMC is constitutively expressed in lung, suggesting a potential role for DMC in recruiting monocytes and dendritic cells from blood into lung parenchyma.

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