Journal
JOURNAL OF IMMUNOLOGY
Volume 197, Issue 11, Pages 4473-4481Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1502640
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Funding
- Dutch Arthritis Foundation
- Dutch Organization for Scientific Research (Vici grant)
- Research Foundation Sole Mio
- Leiden Research Foundation (STROL)
- Centre for Medical Systems Biology
- Innovative Medicines Initiative [115142-2]
- European Union (Seventh Framework Programme integrated project Masterswitch) [223404]
- ReumaFonds [LLP-5] Funding Source: researchfish
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Mast cells (MC) are most well known for their role in innate immune responses. However, MC are increasingly recognized as important regulators of adaptive immune responses, especially in setting the outcome of T cell responses. In this study we determined the effect of MC on cytokine production by naive and memory human Th cells. CD4(+) T cells were cultured with MC supernatant or control medium, after which cytokine production by T cells was determined. Supernatant of activated MC specifically increased the number of IL-17 producing T cells. This enhancement of Th17 cell number was specifically observed for the memory CD4(+) T cell population and not for the naive CD4(+) T cell population. The effect of MC was inhibited for similar to 80% by blocking Abs to IL-1 beta and the rIL-1R antagonist anakinra. Importantly, secretion of active IL-1 beta by MC was independent of caspase activity, indicating that Th17 cell expansion by MC occurred through inflammasome-independent IL-1 beta. Together, these studies reveal a role for human MC in setting the outcome of T cell responses through release of caspase-independent IL-1 beta, and provide evidence for a novel contribution of MC in boosting the Th17 axis in mucosal immune responses.
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