Human IP-9: A keratinocyte-derived high affinity CXC-chemokine ligand for the IP-10/Mig receptor (CXCR3)

C.P. Tensen, J. Flier, E.M.H. van der Raaij-Helmer, S. Sampat-Sardjoepersad, R.C. van der Schors, R. Leurs, R.J. Scheper, D.M. Boorsma, R. Willemze

Research output: Contribution to JournalArticleAcademic

Abstract

Chemokines and their receptors play a crucial part in the recruitment of leukocytes into inflammatory sites. The CXC chemokines IP-10 and Mig are selective attractants for activated (memory) T cells, the predominant cell type in skin infiltrates in many inflammatory dermatoses. The selectivity for activated T cells can be explained by the fact that both chemokines exert their effects through a common receptor, CXCR3, which is nearly exclusively expressed on activated T cells The aim of this study was to identify biologically active CXCR3 ligands produced by keratinocytes. To that end, Chinese hamster ovary cells expressing a cDNA encoding CXCR3 were challenged with proteins obtained from interferon-γ stimulated keratinocytes and subsequently monitored for effects on second messenger systems. By this approach we were able to isolate IP-10 and Mig, and in addition identified a novel highly potent ligand for the CXCR3 receptor, designated interferon-γ- inducible protein-9, which proved to be chemotactic for activated T cells expressing CXCR3. Protein sequence and mass spectrometric analysis followed by molecular cloning of the cDNA encoding interferon-γ-inducible protein-9, revealed that interferon-γ-inducible protein-9 is a CXC chemokine with a molecular mass of 8303 Da. From a GenBank database query it became clear that interferon-γ-inducible protein-9 is in fact the protein encoded by the cDNA sequence also known as β-R1, H174 or I-TAC. In situ hybridization experiments showed that interferon-γ-inducible protein-9 mRNA is expressed by basal layer keratinocytes in a variety of skin disorders, including allergic contact dermatitis, lichen planus, and mycosis fungoides suggesting a functional role for this chemokine in skin immune responses.
Original languageEnglish
Pages (from-to)716-722
JournalJournal of Investigative Dermatology
Volume112
DOIs
Publication statusPublished - 1999

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