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.

Regulatory T cells (Tregs) are critical players of immunological tolerance due to their ability to suppress effector T cell function thereby preventing transplant rejection and autoimmune diseases. During allograft transplantation, increases of both Treg expansion and generation, as well as their stable function, are needed to ensure allograft acceptance; thus, efforts have been made to discover new molecules that enhance Treg-mediated tolerance and to uncover their mechanisms. Recently, vitamin C (VitC), known to regulate T cell maturation and dendritic cell-mediated T cell polarization, has gained attention as a relevant epigenetic remodeler able to enhance and stabilize the expression of the Treg master regulator gene Foxp3, positively affecting the generation of induced Tregs (iTregs). In this study, we measured VitC transporter (SVCT2) expression in different immune cell populations, finding Tregs as one of the cell subset with the highest levels of SVCT2 expression. Unexpectedly, we found that VitC treatment reduces the ability of natural Tregs to suppress effector T cell proliferation in vitro, while having an enhancer effect on TGFβ-induced Foxp3⁺ Tregs. On the other hand, VitC increases iTregs generation in vitro and in vivo, however, no allograft tolerance was achieved in animals orally treated with VitC. Lastly, Tregs isolated from the draining lymph nodes of VitC-treated and transplanted mice also showed impaired suppression capacity ex vivo. Our results indicate that VitC promotes the generation and expansion of Tregs, without exhibiting CD4⁺ T cell-mediated allograft tolerance. These observations highlight the relevance of the nutritional status of patients when immune regulation is needed.

Schizophrenia (SZ), a complex psychiatric disorder of neurodevelopment, is characterised by a range of symptoms, including hallucinations, delusions, social isolation and cognitive deterioration. One of the hypotheses that underlie SZ is related to inflammatory events which could be partly responsible for symptoms. However, it is unknown how inflammatory molecules can contribute to cognitive decline in SZ. This review summarises and exposes the possible contribution of the imbalance between pro-inflammatory and anti-inflammatory interleukins like IL-1beta, IL-4 and TNFalfa among others on cognitive impairment. We discuss how this inflammatory imbalance affects microglia and astrocytes inducing the disruption of the blood–brain barrier (BBB) in SZ, which could impact the prefrontal cortex or associative areas involved in executive functions such as planning and working tasks. We also highlight that inflammatory molecules generated by intestinal microbiota alterations, due to dysfunctional microbial colonisers or the use of some anti-psychotics, could impact the central nervous system. Finally, the question arises as to whether it is possible to modulate or correct the inflammatory imbalance that characterises SZ, and if an immunomodulatory strategy can be incorporated into conventional clinical treatments, either alone or in complement, to be applied in specific phases, such as prodromal or in the first-episode psychosis.

Background: Major depression disorder (MDD) and anxiety are common mental disorders that significantly affect the quality of life of those who suffer from them, altering the person’s normal functioning. From the biological perspective, the most classical hypothesis explaining their occurrence relies on neurotransmission and hippocampal excitability alterations. However, around 30% of MDD patients do not respond to medication targeting these processes. Over the last decade, the involvement of inflammatory responses in depression and anxiety pathogenesis has been strongly acknowledged, opening the possibility of tackling these disorders from an immunological point of view. In this context, regulatory T cells (Treg cells), which naturally maintain immune homeostasis by suppressing inflammation could be promising candidates for their therapeutic use in mental disorders.Methods: To test this hypothesis, C57BL/6 adult male mice were submitted to classical stress protocols to induce depressive and anxiety-like behavior; chronic restriction stress (CRS), and chronic unpredictable stress (CUS). Some of the stressed mice received a single adoptive transfer of Treg cells during stress protocols. Mouse behavior was analyzed through the open field (OFT) and forced swim test (FST). Blood and spleen samples were collected for T cell analysis using cell cytometry, while brains were collected to study changes in microglia by immunohistochemistry.Results: Mice submitted to CRS and CUS develop anxiety and depressive-like behavior, and only CRS mice exhibit lower frequencies of circulating Treg cells. Adoptive transfer of Treg cells decreased anxiety-like behavior in the OFT only in CRS model, but not depressive behavior in FST in neither of the two models. In CRS mice, Treg cells administration lowered the number of microglia in the hippocampus, which increased due this stress paradigm, and restored its arborization. However, in CUS mice, Treg cells administration increased microglia number with no significant effect on their arborization.Conclusion: Our results for effector CD4⁺ T cells in the spleen and microglia number and morphology in the hippocampus add new evidence in favor of the participation of inflammatory responses in the development of depressive and anxiety-like behavior and suggest that the modulation of key immune cells such as Treg cells, could have beneficial effects on these disorders.

Colorectal cancer (CRC) is one of the most diagnosed cancers worldwide, with a high incidence and mortality rate when diagnosed late. Currently, the methods used in healthcare to diagnose CRC are the fecal occult blood test, flexible sigmoidoscopy, and colonoscopy. However, the lack of sensitivity and specificity and low population adherence are driving the need to implement other technologies that can identify biomarkers that not only help with early CRC detection but allow for the selection of more personalized treatment options. In this regard, the implementation of omics technologies, which can screen large pools of biological molecules, coupled with molecular validation, stands out as a promising tool for the discovery of new biomarkers from biopsied tissues or body fluids. This review delves into the current state of the art in the identification of novel CRC biomarkers that can distinguish cancerous tissue, specifically from fecal samples, as this could be the least invasive approach.