title: Expansion of Th17 Cells by Human Mast Cells Is Driven by Inflammasome-Independent IL-1β.
abstract: 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 ∼80% by blocking Abs to IL-1β and the rIL-1R antagonist anakinra. Importantly, secretion of active IL-1β by MC was independent of caspase activity, indicating that Th17 cell expansion by MC occurred through inflammasome-independent IL-1β. Together, these studies reveal a role for human MC in setting the outcome of T cell responses through release of caspase-independent IL-1β, and provide evidence for a novel contribution of MC in boosting the Th17 axis in mucosal immune responses.
authors: Department of Rheumatology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
authors: Jolien
authors: 0000-0002-4092-8925
authors: J
authors: Suurmond
authors: Department of Rheumatology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
authors: Kim L L
authors: 0000-0002-1660-9051
authors: KL
authors: Habets
authors: Department of Rheumatology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
authors: Annemarie L
authors: AL
authors: Dorjée
authors: Department of Rheumatology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
authors: Tom W
authors: TW
authors: Huizinga
authors: Department of Rheumatology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands r.e.m.toes@lumc.nl.
authors: René E M
authors: 0000-0002-9618-6414
authors: RE
authors: Toes
mesh_terms: D057134:Antibodies, Neutralizing / Q000494:pharmacology; D006801:Humans; D018928:Immunity, Mucosal; D058847:Inflammasomes / Q000276:immunology*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; C508585:IL1B protein, human; D058847:Inflammasomes; D053583:Interleukin-1beta