Neuro-endocrine networks controlling immune system in health and disease
The nervous and immune systems have long been considered as compartments that perform separate and different functions. However, recent clinical, epidemiological, and experimental data have suggested that the pathogenesis of several immune-mediated disorders, such as multiple sclerosis (MS), might involve factors, hormones, and neural mediators that link the immune and nervous system. These molecules are members of the same superfamily, which allow the mutual and bi-directional neural–immune interaction. More recently, the discovery of leptin, one of the most abundant adipocyte-derived hormones that control food intake and metabolism, has suggested that nutritional/metabolic status, acting …
Animal models of Multiple Sclerosis
Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) which involves a complex interaction between immune system and neural cells. Animal modeling has been critical for addressing MS pathogenesis. The three most characterized animal models of MS are (1) the experimental autoimmune/allergic encephalomyelitis (EAE); (2) the virally-induced chronic demyelinating disease, known as Theiler׳s murine encephalomyelitis virus (TMEV) infection and (3) the toxin-induced demyelination. All these models, in a complementary way, have allowed to reach a good knowledge of the pathogenesis of MS. Specifically, EAE is the model which better reflects the autoimmu…
Role of adipokines signaling in the modulation of T cells function
The field that links immunity and metabolism is rapidly expanding. Apparently non-immunological disorders such as obesity and type 2 diabetes have been linked to immune dysregulation, suggesting that metabolic alterations can be induced by or be consequence of an altered self-immune tolerance. In this context, adipose tissue produces and releases a variety of pro-inflammatory and anti-inflammatory factors, termed "adipokines," which can be considered as the bridge between obesity-related exogenous factors, such as nutrition and lifestyle, and the molecular events leading to metabolic syndrome, inflammatory, and/or autoimmune conditions. In obesity, increased production of most adipokines im…
Drp1 Controls Effective T Cell Immune-Surveillance by Regulating T Cell Migration, Proliferation, and cMyc-Dependent Metabolic Reprogramming
Summary Mitochondria are key players in the regulation of T cell biology by dynamically responding to cell needs, but how these dynamics integrate in T cells is still poorly understood. We show here that the mitochondrial pro-fission protein Drp1 fosters migration and expansion of developing thymocytes both in vitro and in vivo. In addition, we find that Drp1 sustains in vitro clonal expansion and cMyc-dependent metabolic reprogramming upon activation, also regulating effector T cell numbers in vivo. Migration and extravasation defects are also exhibited in Drp1-deficient mature T cells, unveiling its crucial role in controlling both T cell recirculation in secondary lymphoid organs and acc…