In schistosomiasis, chronic parasite egg–induced granuloma formation can lead to tissue destruction and fibrosis, which causes much of the morbidity and mortality associated with this disease. Here we show the importance of IL-13 in the pathogenesis of schistosomiasis, and demonstrate, perhaps for the first time, the therapeutic efficacy of an IL-13 inhibitor, sIL-13Rα2-Fc, in the control of hepatic fibrosis. T-helper type 2 (Th2) cytokines dominate the immune response in mice infected with Schistosoma mansoni, yet the specific contributions of IL-13 and IL-4 to the development of fibrosis were not previously investigated. Our studies demonstrate that both cytokines play redundant roles in granuloma formation, which explains the ability of IL-4–deficient mice to form granulomas around eggs. More importantly, however, these studies demonstrate that IL-13 is the dominant Th2-type cytokine regulating fibrosis. IL-13 stimulated collagen production in fibroblasts, and procollagen I and procollagen III mRNA expression was decreased in sIL-13Rα2-Fc–treated mice. Moreover, the reduction in fibrosis observed in IL-4–deficient mice was much less pronounced than that in sIL-13Rα2-Fc–treated animals. Fibrosis is a major pathological manifestation of a number of allergic, autoimmune, and infectious diseases. Thus, our findings provide evidence that IL-13 inhibitors may be of general therapeutic benefit in preventing damaging tissue fibrosis resulting from Th2-dominated inflammatory responses.
Mónica G. Chiaramonte, Debra D. Donaldson, Allen W. Cheever, Thomas A. Wynn
Title and authors | Publication | Year |
---|---|---|
Type 2 Cysteinyl Leukotriene Receptors Drive IL-33–Dependent Type 2 Immunopathology and Aspirin Sensitivity
T Liu, NA Barrett, Y Kanaoka, E Yoshimoto, D Garofalo, H Cirka, C Feng, JA Boyce |
Journal of immunology (Baltimore, Md. : 1950) | 2017 |
The Immunology of Cardiovascular Homeostasis and Pathology
S Sattler, T Kennedy-Lydon |
The Immunology of Cardiovascular Homeostasis and Pathology | 2017 |
The Immunology of Cardiovascular Homeostasis and Pathology
S Sattler, T Kennedy-Lydon |
The Immunology of Cardiovascular Homeostasis and Pathology | 2017 |
Recruited Monocytes and Type 2 Immunity Promote Lung Regeneration following Pneumonectomy
AJ Lechner, IH Driver, J Lee, CM Conroy, A Nagle, RM Locksley, JR Rock |
Cell Stem Cell | 2017 |
Radiation-Induced Fibrosis: Mechanisms and Opportunities to Mitigate. Report of an NCI Workshop, September 19, 2016
DE Citrin, PG Prasanna, AJ Walker, ML Freeman, I Eke, MH Barcellos-Hoff, MJ Arankalayil, EP Cohen, RC Wilkins, MM Ahmed, MS Anscher, B Movsas, JC Buchsbaum, MS Mendonca, TA Wynn, CN Coleman |
Radiation Research | 2017 |
Dioscin Exerts Protective Effects Against Crystalline Silica-induced Pulmonary Fibrosis in Mice
C Li, Y Lu, S Du, S Li, Y Zhang, F Liu, Y Chen, D Weng, J Chen |
Theranostics | 2017 |
Review: Frontiers of Antifibrotic Therapy in Systemic Sclerosis: ANTIFIBROTIC THERAPY IN SSc
JH Distler, C Feghali-Bostwick, A Soare, Y Asano, O Distler, DJ Abraham |
Arthritis & Rheumatology | 2017 |
Hydrolysis of Hyaluronic Acid in Lymphedematous Tissue Alleviates Fibrogenesis via TH1 Cell-Mediated Cytokine Expression
S Cho, K Roh, J Park, YS Park, M Lee, S Cho, EJ Kil, MJ Cho, JS Oh, HS Byun, SH Cho, K Park, H Kang, J Koo, CH Yeom, S Lee |
Scientific Reports | 2017 |
Clonorchis sinensis lysophospholipase A upregulates IL-25 expression in macrophages as a potential pathway to liver fibrosis
L Zhou, M Shi, L Zhao, Z Lin, Z Tang, H Sun, T Chen, Z Lv, J Xu, Y Huang, X Yu |
Parasites & vectors | 2017 |
Type 2 immunity in tissue repair and fibrosis
RL Gieseck, MS Wilson, TA Wynn |
Nature Reviews Immunology | 2017 |
Stromal and immune cells in gut fibrosis: the myofibroblast and the scarface
V Valatas |
Annals of Gastroenterology | 2017 |
Host regulation of liver fibroproliferative pathology during experimental schistosomiasis via interleukin-4 receptor alpha
JK Nono, H Ndlovu, NA Aziz, T Mpotje, L Hlaka, F Brombacher, SJ Davies |
PLoS neglected tropical diseases | 2017 |
A comparative analysis of the molecular basis of fibrosis between tissues
R Miller, M Fell, J Pleat |
Comparative Clinical Pathology | 2017 |
Therapeutic pro-fibrogenic signaling pathways in fibroblasts
S Cannito, E Novo, M Parola |
Advanced Drug Delivery Reviews | 2017 |
Radiation-Induced Fibrosis: Mechanisms and Opportunities to Mitigate. Report of an NCI Workshop, September 19, 2016
DE Citrin, PG Prasanna, AJ Walker, ML Freeman, I Eke, MH Barcellos-Hoff, MJ Arankalayil, EP Cohen, RC Wilkins, MM Ahmed, MS Anscher, B Movsas, JC Buchsbaum, MS Mendonca, TA Wynn, CN Coleman |
Radiation Research | 2017 |
Thoracic Irradiation Recruit M2 Macrophage into the Lung, Leading to Pneumonitis and Pulmonary Fibrosis
HR Park, SK Jo, U Jung |
2017 |