IL-22BP is produced by eosinophils in human gut and blocks IL-22 protective actions during colitis.
Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel diseases (IBDs), are characterized by high levels of IL-22 production. Rodent studies revealed that this cytokine is protective during colitis but whether this is true in IBDs is unclear. We show here that levels of the soluble inhibitor of IL-22, interleukin 22-binding protein (IL-22BP), are significantly enhanced during IBDs owing to increased numbers of IL-22BP-producing eosinophils, that we unexpectedly identify as the most abundant source of IL-22BP protein in human gut. In addition, using IL-22BP-deficient rats, we confirm that endogenous IL-22BP is effective at blocking protective actions of IL-22 during acute colitis. In conclusion, our study provides new important insights regarding the biology of IL-22 and IL-22BP in the gut and indicates that protective actions of IL-22 are likely to be suboptimal in IBDs thus making IL-22BP a new relevant therapeutic target.
INSERM Center for Research in Transplantation and Immunology, UMR1064, ITUN, Nantes, France.|Université de Nantes, Faculté de Médecine, Nantes, France.|CHU Nantes, Laboratoire d'Immunologie, Nantes, France.
J C
JC
Martin
INSERM Center for Research in Transplantation and Immunology, UMR1064, ITUN, Nantes, France.
G
G
Bériou
INSERM Center for Research in Transplantation and Immunology, UMR1064, ITUN, Nantes, France.
M
M
Heslan
Université de Nantes, Faculté de Médecine, Nantes, France.|EA4273 Biometadys, Faculté de Médecine, Université de Nantes, Nantes, France.|CHU Nantes, Laboratoire d'anatomopathologie, Nantes, France.
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C
Bossard
EA4273 Biometadys, Faculté de Médecine, Université de Nantes, Nantes, France.
A
A
Jarry
INSERM Center for Research in Transplantation and Immunology, UMR1064, ITUN, Nantes, France.
A
A
Abidi
Plateforme MicroPICell, SFR santé, Nantes, France.
P
P
Hulin
INSERM Center for Research in Transplantation and Immunology, UMR1064, ITUN, Nantes, France.
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S
Ménoret
INSERM Center for Research in Transplantation and Immunology, UMR1064, ITUN, Nantes, France.
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R
Thinard
INSERM Center for Research in Transplantation and Immunology, UMR1064, ITUN, Nantes, France.
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I
Anegon
EA3826, Faculté de Médecine, Université de Nantes, Nantes, France.
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C
Jacqueline
Institut des Maladies de l'Appareil Digestif - IMAD, INSERM UMR913, Nantes, France.
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B
Lardeux
INSERM Center for Research in Transplantation and Immunology, UMR1064, ITUN, Nantes, France.
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F
Halary
Ludwig Institute for Cancer Research, Brussels, Belgium.|Institut de Duve, Université catholique de Louvain, Brussels, Belgium.
J-C
JC
Renauld
Institut des Maladies de l'Appareil Digestif - IMAD, INSERM UMR913, Nantes, France.|Institut des Maladies de l'Appareil Digestif - IMAD, INSERM CIC-04, CHU Nantes, Nantes, France.
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A
Bourreille
INSERM Center for Research in Transplantation and Immunology, UMR1064, ITUN, Nantes, France.|Université de Nantes, Faculté de Médecine, Nantes, France.|CHU Nantes, Laboratoire d'Immunologie, Nantes, France.
R
R
Josien
D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000473:pathology; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D000097043:Interleukin-22
D016264:Dextran Sulfate; D007378:Interleukins; D018123:Receptors, Interleukin; D000097043:Interleukin-22; C433253:IL22RA2 protein, human; C415369:interleukin-22 receptor