A80 MALT1 BLOCKS IL-1β-MEDIATED INTESTINAL INFLAMMATION

Abstract

Background: Primary immune deficiencies are often accompanied by intestinal inflammation. A patient with severe combined immunodeficiency and dramatic inflammation along the gastrointestinal tract was diagnosed with a homozygous mutation in MALT1. Malt1 acts both as a scaffolding protein and a protease. The consequences of MALT1 immunodeficiency have largely been attributed to its role in lymphocytes. However, macrophages play an important role in gut inflammation and Malt1 is activated in macrophages downstream of toll-like receptor 4 and dectin-1. The effect of MALT1 deficiency in macrophages and its contribution to gut inflammation has not been investigated. Aims: We hypothesized that Malt1 deficiency in murine macrophages increases susceptibility to DSS-induced colitis by increasing pro-inflammatory cytokine production. To address this hypothesis, we will determine: 1) whether Malt1 deficient mice are more susceptible to DSS-induced intestinal inflammation than wild type mice, and 2) the role of Malt1 expression and activity in pro-inflammatory macrophage responses. Methods: Malt1+/+ and Malt1 -/-mice were subjected to DSS-induced colitis and sacrificed for histology, immunohistochemistry, and tissue cytokine analyses by ELISA. Malt1 +/+ or Malt1