Intestinal mononuclear cells primed by systemic interleukin‐12 display long‐term ability to aggravate colitis in mice

• Published in: Immunology Vol. 150; no. 3; pp. 290 - 300
• Main Authors: Pedrotti, Luciano P., Sena, Angela A., Rodriguez Galán, María Cecilia, Cejas, Hugo, Correa, Silvia G.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.03.2017; John Wiley and Sons Inc
• Subjects: Animals; Cells, Cultured; colitis; Colitis - chemically induced; Colitis - immunology; Colon; Colon - immunology; Cytokines; Dextran Sulfate; DNA, Complementary - administration & dosage; Humans; Inflammatory bowel disease; Inflammatory Bowel Diseases - immunology; Interleukin-12 Subunit p35 - genetics; Interleukin-12 Subunit p40 - genetics; interleukin‐12; Intestinal Mucosa - immunology; Leukocytes, Mononuclear - immunology; macrophage; Mice; Mice, Inbred C57BL; Monocytes - immunology; Original; priming; Recombinant Fusion Proteins - metabolism; Rodents; systemic T cell; Vaccines, DNA - immunology; systemic T cell; priming; macrophage; colitis; interleukin-12
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/imm.12685

Summary To address whether the burst of systemic interleukin‐12 (IL‐12) influences intestinal inflammation elicited by luminal stimuli, we induced IL‐12 release by cDNA injection in C57BL/6 mice and simultaneously started dextran sulphate sodium administration. The sequence of the inflammatory response triggered by IL‐12 release was characterized by assessing myeloperoxidase activity and histological damage in colon samples on days 1, 3, 5 and 7 after colitis induction. To evaluate the persistence of IL‐12 priming, colitis was induced in mice 7 or 60 days after cDNA injection. Under IL‐12 influence, the development of acute colitis presented a faster and selective infiltration of inflammatory mononuclear cells in the lamina propria. Recruitment was driven by systemic cytokines rather than luminal antigens. Interestingly, when colitis was triggered 7 or 60 days after the cytokine storm, cells maintained the ability to worsen clinical signs of intestinal inflammation. Together, a systemic IL‐12 burst effectively primed intestinal cells that became more prone to develop inflammatory responses. Activation was long‐lasting because intestinal cells maintained their inflammatory potential and their ability to aggravate colitis. Systemic interleukin‐12 promotes acute colitis with a predominant mononuclear inflammation in the lamina propria. When colitis is triggered 7 or 60 days after the cytokine storm, primed cells keep the ability to worsen clinical signs of intestinal inflammation.