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Gene expression profiling of rat jejunum treated with MLT-943, a small molecule MALT1 protease inhibitor

ABSTRACT: MALT1 protease inhibition is effective in several preclinical models of autoimmunity and B cell malignancies. However, severe reduction in regulatory T cells (Tregs) and an associated IPEX-like pathology was observed in mice with congenital deficiency of MALT1. Rats treated with MLT-943, a novel potent and selective MALT1 inhibitor showed a rapid and dose-dependent reduction in Tregs and resulted in the progressive appearance of immune abnormalities and clinical signs of an IPEX-like pathology, including severe intestinal inflammation associated with mast cell activation, high serum IgE levels, systemic T cell activation and mononuclear cell infiltration in multiple tissues. Gene expression profiling of rat jejunum was performed to understand the molecular events related to the aforementioned morphological changes. MLT-943 induced a dose-dependent up-regulation of a mast cell, cytotoxic T cells and interferon signatures in rat jejunum. Of note, T cells and IFNγ were described as major drivers of the pathology occurring in MALT1 protease dead animals.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Elaine Tritto

PROVIDER: E-MTAB-8990 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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