Human eosinophils produce the T cell-attracting chemokines MIG and IP-10 upon stimulation with IFN-

Abstract: Eosinophils participate in allergic in-flammation, where expression of T helper cell type 2 (Th2) cytokines such as interleukin (IL)-4 and IL-5 are seen. However, eosinophils sometimes ac-cumulate during disease with expression of Th1 cytokines [i.e., interferon- (IFN-), tumor necro-sis factor (TNF-), and IL-1]. In this study, we investigated whether eosinophils can respond with expression of the IFN-inducible C–X–C chemokine monokines induced by IFN- [MIG; CXC chemo-kine ligand 9 (CXCL9)], IFN--inducible protein (IP-10/CXCL10), and IFN-inducible T cell che-moattractant (I-TAC/CXCL11). These chemokines share the ability to recruit and activate T cells and natural killer cells to sites of inflammation. We found that IFN- induced rapid and sustained gene expression of MIG, IP-10, and I-TAC in eosino-phils, as detected by quantitative reverse transcrip-tase-polymerase chain reaction. During incuba-tion, IFN--stimulated eosinophils released MIG and IP-10, as detected by enzyme-linked immu-nosorbent assay, and I-TAC could not be detected in the medium. TNF- but not IL-1 enhanced the IFN--induced production of MIG and IP-10. Con-versely, addition of the Th2 cytokine IL-4 down-regulated IFN--induced synthesis of MIG and IP–10 in eosinophils. Crohn’s disease is character-ized by a Th1-polarized inflammation and presence of eosinophils. In lesions from this disease, MIG was detected in eosinophils by immunohistochem-istry. Taken together, the results point to immuno-regulatory roles for eosinophils during some dis-eases with Th1-polarized inflammation. J. Leukoc