Abstract:
:MPhi and DC are key elements in the control of tissue homeostasis and response to insult. In this work, we demonstrate that MPhi 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 MPhi 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-kappaB and/or STAT1. B cells also express IL4I1 in response to NF-kappaB-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.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Marquet J,Lasoudris F,Cousin C,Puiffe ML,Martin-Garcia N,Baud V,Chereau F,Farcet JP,Molinier-Frenkel V,Castellano Fdoi
10.1002/eji.201040428subject
Has Abstractpub_date
2010-09-01 00:00:00pages
2557-68issue
9eissn
0014-2980issn
1521-4141journal_volume
40pub_type
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