Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 40, Issue 9, Pages 2557-2568Publisher
WILEY
DOI: 10.1002/eji.201040428
Keywords
Granuloma; Immunosuppressive Enzyme; Inflammation; NF-kappa B; STAT
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Funding
- ARC [4883]
- ANR
- ARC
- Belgian InterUniversity Attraction Pole
- Canceropole Ile-de-France
- Institut National du Cancer
- Amgen
- Roche France
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M Phi and DC are key elements in the control of tissue homeostasis and response to insult. In this work, we demonstrate that M Phi and DC are the major producers of the phenylalanine catabolizing enzyme IL-4-induced gene 1 (IL4I1) under inflammatory conditions. IL4I1 was first described in B cells, which indeed can produce IL4I1 in vitro, although at much lower levels. In vivo, IL4I1 is highly expressed by M Phi and DC of Th1 granulomas (sarcoidosis, tuberculosis) but poorly detected in Th2 granulomas (schistosomiasis). In vitro, expression of the enzyme is induced in mononuclear phagocytes by various pro-inflammatory stimuli through the activation of the transcription factors NF-kappa B and/or STAT1. B cells also express IL4I1 in response to NF-kappa B-activating stimuli such as CD40L; however, in contrast to myeloid cells, B cells are insensitive to IFN-gamma but respond to stimulation of the IL-4/STAT6 axis. As we show that the expression of IL4I1 by a monocytic cell line inhibits T-cell proliferation and production of IFN-gamma and inflammatory cytokines, we propose that IL4I1 participates in the downregulation of Th1 inflammation in vivo.
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