ABSTRACT
Nutritional signals have long been implicated in the control of cellular processes that take place in the hypothalamus. This includes food intake regulation and energy balance, inflammation, and most recently, neurogenesis. One of the main glial cells residing in the hypothalamus are tanycytes, radial glial-like cells, whose bodies are located in the lining of the third ventricle, with processes extending to the parenchyma and reaching neuronal nuclei. Their unique anatomical location makes them directly exposed to nutrients in the cerebrospinal fluid. Several research groups have shown that tanycytes can respond to nutritional signals by different mechanisms, such as calcium signaling, metabolic shift, and changes in proliferation/differentiation potential. Despite cumulative evidence showing tanycytes have the molecular components to participate in nutrient detection and response, there are no enough functional studies connecting tanycyte nutrient sensing with hypothalamic functions, nor that highlight the relevance of this process in physiological and pathological context. This review will summarize recent evidence that supports a nutrient sensor role for tanycytes in the hypothalamus, highlighting the need for more detailed analysis on the actual implications of tanycyte-nutrient sensing and how this process can be modulated, which might allow the discovery of new metabolic and signaling pathways as therapeutic targets, for the treatment of hypothalamic related diseases.
ABSTRACT
In the last years, mesenchymal stem cell (MSC)-based therapies have become an interesting therapeutic opportunity for the treatment of rheumatoid arthritis (RA) due to their capacity to potently modulate the immune response. RA is a chronic autoimmune inflammatory disorder with an incompletely understood etiology. However, it has been well described that peripheral tolerance defects and the subsequent abnormal infiltration and activation of diverse immune cells into the synovial membrane, are critical for RA development and progression. Moreover, the imbalance between the immune response of pro-inflammatory and anti-inflammatory cells, in particular between memory Th17 and memory regulatory T cells (Treg), respectively, is well admitted to be associated to RA immunopathogenesis. In this context, MSCs, which are able to alter the frequency and function of memory lymphocytes including Th17, follicular helper T (Tfh) cells and gamma delta (γδ) T cells while promoting Treg cell generation, have been proposed as a candidate of choice for RA cell therapy. Indeed, given the plasticity of memory CD4+ T cells, it is reasonable to think that MSCs will restore the balance between pro-inflammatory and anti-inflammatory memory T cells populations deregulated in RA leading to prompt their therapeutic function. In the present review, we will discuss the role of memory T cells implicated in RA pathogenesis and the beneficial effects exerted by MSCs on the phenotype and functions of these immune cells abnormally regulated in RA and how this regulation could impact RA progression.
