ABSTRACT
Chitin and its derivative chitosan (Q) are abundant structural elements in nature. Q has modulatory and anti-inflammatory effects and also regulates the expression of adhesion molecules. The interaction between cells expressing the αEß7 integrin and E-cadherin facilitates tolerogenic signal transmission and localization of lymphocytes at the frontline for interaction with luminal antigens. In this study we evaluated the ability of orally administered Q to stimulate E-cadherin and CD103 expression in vitro and in vivo. Our findings show that Q promoted epithelial cell migration, accelerated wound healing and increased E-cadherin expression in IEC-18 cells and isolated intestinal epithelial cells (IECs) after Q feeding. The upregulation of E-cadherin was dependent on TLR4 and IFNAR signaling, triggering CD103 expression in lymphocytes. Q reinforced the E-cadherin-αEß7 axis, crucial for intestinal barrier integrity and contributed to the localization of lymphocytes on the epithelium.
Subject(s)
Antigens, CD , Cadherins , Chitosan , Integrin alpha Chains , Intestinal Mucosa , Signal Transduction , Toll-Like Receptor 4 , Animals , Toll-Like Receptor 4/metabolism , Chitosan/pharmacology , Chitosan/chemistry , Cadherins/metabolism , Signal Transduction/drug effects , Integrin alpha Chains/metabolism , Mice , Antigens, CD/metabolism , Intestinal Mucosa/metabolism , Intestinal Mucosa/drug effects , Cell Movement/drug effects , Cell Line , Intestines/drug effects , Rats , MaleABSTRACT
While positive social-behavioral factors predict longer survival in cancer patients, the underlying mechanisms are unknown. Since tumor metastasis are the major cancer mortality factor, we investigated how an enriched environment (EE) conductive to enhanced sensory, cognitive and motor stimulation impact metastatic progression in lungs following intravasation in the circulation. We find that mice housed in EE exhibited reduced number of lung metastatic foci compared to control mice housed in a standard environment (SE). Compared to SE mice, EE mice increased lung inflammation as early as 4 days after circulating tumor cells extravasation. The impact of environmental signals on lung metastasis is independent of adrenergic receptors signaling. By contrast, we find that serum corticosterone levels are lower in EE mice and that glucocorticoid receptor (GR) antagonist reduces the number of lung metastasis in SE mice. In addition, the difference of the number of lung metastasis between SE and EE mice is abolished when inflammatory monocytes are rendered deficient in GR signaling. This decreased GR signaling in inflammatory monocytes of SE mice results in an exacerbated inflammatory profile in the lung. Our study shows that not only EE reduces late stages of metastatic progression in lungs but disclose a novel anti-tumor mechanism whereby GR-dependent reprogramming of inflammatory monocytes can inhibit metastatic progression in lungs. Moreover, while inflammatory monocytes have been shown to promote cancer progression, they also have an anti-tumor effect, suggesting that their role is more complex than currently thought.
ABSTRACT
Enriched environment (EE) induces plasticity changes in the brain. Recently, CD4+ T cells have been shown to be involved in brain plasticity processes. Here, we show that CD8+ T cells are required for EE-induced brain plasticity in mice, as revealed by measurements of hippocampal volume, neurogenesis in the DG of the hippocampus, spinogenesis and glutamatergic synaptic function in the CA of the hippocampus. As a consequence, EE-induced behavioral benefits depend, at least in part, on CD8+ T cells. In addition, we show that spleen CD8+ T cells from mice housed in standard environment (SE) and EE have different properties in terms of 1) TNFα release after in vitro CD3/CD28 or PMA/Iono stimulation 2) in vitro proliferation properties 3) CD8+ CD44+ CD62Llow and CD62Lhi T cells repartition 4) transcriptomic signature as revealed by RNA sequencing. CD8+ T cells purified from the choroid plexus of SE and EE mice also exhibit different transcriptomic profiles as highlighted by single-cell mRNA sequencing. We show that CD8+ T cells are essential mediators of beneficial EE effects on brain plasticity and cognition. Additionally, we propose that EE differentially primes CD8+ T cells leading to behavioral improvement.
Subject(s)
Behavior, Animal/physiology , CD8-Positive T-Lymphocytes/metabolism , Environment , Hippocampus/physiology , Neurogenesis/physiology , Neuronal Plasticity/physiology , Animals , Cell Proliferation/physiology , Feeding Behavior/physiology , Female , Mice , Motor Activity/physiologyABSTRACT
Las superficies mucosas del organismo representan los principales sitios de exposición a antígenos extraños. La mayor densidad antigénica se presenta a nivel del intestino, en donde un epitelio absortivo simple está expuesto a macromoléculas provenientes de la alimentos y bactarias entéricas integras o derivados de su actividad metaólica. El intestino humano aloja aproximadamente 10 bacterias que resultan esenciales para la salud. Años de coevolución han amalgamdo una relación simbiótica hospedador-microbio en la que las bacterias intestinales contribuyen al emtabolismo en cambio ocupan un nicho rico en nutrientes. Las células del epitelio intestinal representan el limíte físico del hospedador y desarrollan mecanismos altamente efectivos para regular el grado de interacción hospedador-microbiota.
