Dichotomy between factors inducing the immunosuppressive enzyme IL-4-induced gene 1 (IL4I1) in B lymphocytes and mononuclear phagocytes.
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.
Marquet
Jeanine
J
INSERM, Unité 955, IMRB, eq 09, Créteil, France.
Lasoudris
Fanette
F
Cousin
Céline
C
Puiffe
Marie-Line
ML
Martin-Garcia
Nadine
N
Baud
Véronique
V
Chereau
Fanny
F
Farcet
Jean-Pierre
JP
Molinier-Frenkel
Valérie
V
Castellano
Flavia
F
D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D023201:CD40 Ligand / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation; D018920:Coculture Techniques; D005420:Flavoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D050830:L-Amino Acid Oxidase; D012157:Mononuclear Phagocyte System / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D005420:Flavoproteins; D016328:NF-kappa B; D034741:RNA, Small Interfering; D050794:STAT1 Transcription Factor; D050800:STAT6 Transcription Factor; D023201:CD40 Ligand; D015847:Interleukin-4; D007371:Interferon-gamma; C484538:Il4i1 protein, mouse; D050830:L-Amino Acid Oxidase