Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology
| Autor: | Brent S. McKenzie, Daniel J. Cua, Barbara Joyce-Shaikh, Nicolas Robinson, Fiona Powrie, Holm H. Uhlig, Sophie Hue, Renata Stepankova, Helena Tlaskalova-Hogenova, Claire Thompson, Sofia Buonocore |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Pathology
medicine.medical_specialty medicine.medical_treatment Immunology HUMDISEASE Biology Systemic inflammation Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine Immune system Interleukin 23 medicine Immunology and Allergy 030304 developmental biology 0303 health sciences Innate immune system Innate lymphoid cell 3. Good health Cytokine Infectious Diseases Mucosal immunology CELLIMMUNO medicine.symptom 030215 immunology |
| Popis: | The CD40-CD154 pathway is important in the pathogenesis of inflammatory bowel disease. Here we show that injection of an agonistic CD40 mAb to T and B cell-deficient mice was sufficient to induce a pathogenic systemic and intestinal innate inflammatory response that was functionally dependent on tumor necrosis factor-alpha and interferon-gamma as well as interleukin-12 p40 and interleukin-23 p40 secretion. CD40-induced colitis, but not wasting disease or serum proinflammatory cytokine production, depended on interleukin-23 p19 secretion, whereas interleukin-12 p35 secretion controlled wasting disease and serum cytokine production but not mucosal immunopathology. Intestinal inflammation was associated with IL-23 (p19) mRNA-producing intestinal dendritic cells and IL-17A mRNA within the intestine. Our experiments identified IL-23 as an effector cytokine within the innate intestinal immune system. The differential role of IL-23 in local but not systemic inflammation suggests that it may make a more specific target for the treatment of IBD. |
| Databáze: | OpenAIRE |
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