title: IL-22 induces an acute-phase response.
abstract: IL-22 is made by a unique set of innate and adaptive immune cells, including the recently identified noncytolytic NK, lymphoid tissue-inducer, Th17, and Th22 cells. The direct effects of IL-22 are restricted to nonhematopoietic cells, its receptor expressed on the surface of only epithelial cells and some fibroblasts in various organs, including parenchymal tissue of the gut, lung, skin, and liver. Despite this cellular restriction on IL-22 activity, we demonstrate that IL-22 induces effects on systemic biochemical, cellular, and physiological parameters. By utilizing adenoviral-mediated delivery of IL-22 and systemic administration of IL-22 protein, we observed that IL-22 modulates factors involved in coagulation, including fibrinogen levels and platelet numbers, and cellular constituents of blood, such as neutrophil and RBC counts. Furthermore, we observed that IL-22 induces thymic atrophy, body weight loss, and renal proximal tubule metabolic activity. These cellular and physiological parameters are indicative of a systemic inflammatory state. We observed that IL-22 induces biochemical changes in the liver including induction of fibrinogen, CXCL1, and serum amyloid A that likely contribute to the reported cellular and physiological effects of IL-22. Based on these findings, we propose that downstream of its expression and impact in local tissue inflammation, circulating IL-22 can further induce changes in systemic physiology that is indicative of an acute-phase response.
authors.affiliation: Inflammation and Immunology Research Unit, Pfizer Biotherapeutics Research and Development, Cambridge, MA 02140, USA.
authors.forename: Spencer C
authors.initials: SC
authors.lastname: Liang
authors.forename: Cheryl
authors.initials: C
authors.lastname: Nickerson-Nutter
authors.forename: Debra D
authors.initials: DD
authors.lastname: Pittman
authors.forename: Yijun
authors.initials: Y
authors.lastname: Carrier
authors.forename: Debra G
authors.initials: DG
authors.lastname: Goodwin
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Shields
authors.forename: Andre-Jean
authors.initials: AJ
authors.lastname: Lambert
authors.forename: Scott H
authors.initials: SH
authors.lastname: Schelling
authors.forename: Quintus G
authors.initials: QG
authors.lastname: Medley
authors.forename: Hak-Ling
authors.initials: HL
authors.lastname: Ma
authors.forename: Mary
authors.initials: M
authors.lastname: Collins
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Dunussi-Joannopoulos
authors.forename: Lynette A
authors.initials: LA
authors.lastname: Fouser
mesh_terms: D000210:Acute-Phase Reaction / Q000276:immunology* / Q000503:physiopathology*; D000818:Animals; D007378:Interleukins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D000097043:Interleukin-22