Role of Immuno-Responsive Gene-1 in regulating Efferocytosis in Mouse Model of EAE

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B869
Abstract ID: 5487

Presenting Author:
Mohammad Nematullah , Post Doctoral Fellow at Henry Ford Hlth.

Abstract:

Multiple sclerosis (MS) is a condition characterized by inflammation and demyelination, primarily affecting individuals in their youth. Numerous studies have documented the buildup of dying cells and myelin debris in the CNS, leading to inflammation and disability. This suggests that enhancing the removal of cellular debris could be a promising approach to address disability and promote the restoration of myelin. Efferocytosis is a process in which phagocytes take in apoptotic cells and help maintain tissue balance by releasing anti-inflammatory cytokines. However, the relationship between efferocytosis and EAE pathogenesis is not well understood. Loss of Irg1 is expected to interfere with the efferocytosis process, causing a strong inflammatory environment in the CNS, which in turn impairs disease resolution. We observed that Irg1 knockout displayed more severe experimental autoimmune encephalomyelitis (EAE) disease compared to wild type. Further, macrophages lacking Irg1 showed upregulation in the levels of NLRP3, GSDMD,and IL1β, along with a decrease in the phagocytic activity. Also, it showed reduced expression of key efferocytosis genes such MerTk, CD206, and arginase 1, suggesting that a lack of Irg1 leads to a highly inflammatory environment, resulting in impaired efferocytosis. Our results indicate that directing interventions towards the Irg1 gene could surpass the constraints of existing drugs and open possibilities for novel techniques in the treatment of MS.