DOI: 10.1101/475517Nov 26, 2018Paper

T cells instruct dendritic cells to produce inflammasome independent IL-1β causing systemic inflammation

BioRxiv : the Preprint Server for Biology
Aakanksha JainChandrashekhar Pasare

Abstract

While IL-1β is critical for anti-microbial host defense, it is also a key mediator of autoimmune inflammation. Inflammasome activation following pathogenic insults is known to result in IL-1β production. However, the molecular events that produce IL-1β during T cell driven autoimmune diseases remain unclear. Here, we have discovered an inflammasome-independent pathway of IL-1β production that is triggered upon cognate interactions between dendritic cells and effector CD4 T cells. Analogous to inflammasome activation, this T cell-instructed IL-1β also relies on two independent signaling events. TNFα produced by activated CD4 T cells engages TNFR signaling on DCs leading to pro-IL-1β synthesis. Subsequently, FasL, also expressed by effector CD4 T cells, engages Fas on DCs leading to caspase-8 dependent pro-IL-1β cleavage. Remarkably, this two-step mechanism is completely independent of pattern recognition receptor activation. IL-1β produced upon cognate DC-effector CD4 T cell interaction causes wide spread leukocyte infiltration, a hallmark of systemic inflammation as well as autoimmune pathology. This study has uncovered a novel feature of DC-T cell cross-talk that allows for active IL-1β secretion independent of innate sensing ...Continue Reading

Related Concepts

Autoimmune Diseases
Autoimmunity
Dendritic Cells
Interleukin-1 beta
T-Lymphocyte
CD4 Positive T Lymphocytes
Tumor Necrosis Factor Receptor
Leucocytic Infiltrate
Patterns
Caspase-8

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