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Published on: June 23, 2013
The IL-21 receptor augments Th2 effector function and alternative macrophage activation
John Pesce1, Mallika Kaviratne, Thirumalai R Ramalingam
1Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, Maryland 20892, USA.
The Interleukin-21 receptor (IL-21R) amplifies T helper 2 (Th2) immune responses. Blocking IL-21R reduces inflammation and fibrosis in parasitic infections, suggesting therapeutic potential.
Area of Science:
- Immunology
- Inflammation and Fibrosis Research
Background:
- The Interleukin-21 receptor (IL-21R) shares homology with the Interleukin-4 receptor (IL-4R).
- CD4+ T helper 2 (Th2) cells are a key source of IL-21.
Purpose of the Study:
- To investigate the role of IL-21R in regulating Th2 responses in vivo.
- To assess the impact of IL-21R deficiency on Th2-dependent pathology during parasitic infections.
Main Methods:
- Infection of IL-21R knockout (IL-21R-/-) mice with Schistosoma mansoni and Nippostrongylus brasiliensis.
- Treatment of wild-type mice with soluble IL-21R-Fc fusion protein.
- In vitro analysis of macrophage activation and cytokine expression.
Main Results:
- Significantly reduced granulomatous inflammation and liver fibrosis in IL-21R-/- mice infected with S. mansoni.
- Impaired Th2 cytokine (IL-4, IL-13) expression and function, including reduced AMCase, Ym1, and FIZZ1 (RELMalpha) responses.
- IL-21 enhanced macrophage expression of IL-4Ralpha and IL-13Ralpha1, boosting FIZZ1 and arginase-1 activity in response to IL-4 and IL-13.
Conclusions:
- IL-21R acts as a crucial amplifier of alternative macrophage activation.
- IL-21R plays an essential role in the development of pathogen-induced Th2 responses.
- Targeting IL-21R may offer therapeutic strategies for inflammatory and fibrotic diseases.
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