Feeding Our Immune System: Impact on Metabolism

Endogenous intestinal microflora and environmental factors, such as diet, play a central role in immune homeostasis and reactivity. In addition, microflora and diet both influence body weight and insulin-resistance, notably through an action on adipose cells. Moreover, it is known since a long time that any disturbance in metabolism, like obesity, is associated with immune alteration, for example, inflammation. The purpose of this review is to provide an update on how nutrients-derived factors (mostly focusing on fatty acids and glucose) impact the innate and acquired immune systems, including the gut immune system and its associated bacterial flora. We will try to show the reader how the highly energy-demanding immune cells use glucose as a main source of fuel in a way similar to that of insulin-responsive adipose tissue and how Toll-like receptors (TLRs) of the innate immune system, which are found on immune cells, intestinal cells, and adipocytes, are presently viewed as essential actors in the complex balance ensuring bodily immune and metabolic health. Understanding more about these links will surely help to study and understand in a more fundamental way the common observation that eating healthy will keep you and your immune system healthy

Interleukin-7, a New Cytokine Targeting the Mouse Hypothalamic Arcuate Nucleus: Role in Body Weight and Food Intake Regulation

Body weight is controlled through peripheral (white adipose tissue) and central (mainly hypothalamus) mechanisms. We have recently obtained evidence that overexpression of interleukin (IL)-7, a critical cytokine involved in lymphopoiesis, can protect against the development of diet-induced obesity in mice. Here we assessed whether IL-7 mediated its effects by modulating hypothalamic function. Acute subcutaneous injection of IL-7 prevented monosodium glutamate-induced obesity, this being correlated with partial protection against cell death in the hypothalamic arcuate nucleus (ARC). Moreover, we showed that IL-7 activated hypothalamic areas involved in regulation of feeding behavior, as indicated by induction of the activation marker c-Fos in neural cells located in the ventromedial part of the ARC and by inhibition of food intake after fasting. Both chains of the IL-7 receptor (IL-7Rα and γc) were expressed in the ARC and IL-7 injection induced STAT-3 phosphorylation in this area. Finally, we established that IL-7 modulated the expression of neuropeptides that tune food intake, with a stimulatory effect on the expression of pro-opiomelanocortin and an inhibitory effect on agouti-related peptide expression in accordance with IL-7 promoting anorectic effects. These results suggest that the immunomodulatory cytokine IL-7 plays an important and unappreciated role in hypothalamic body weight regulation

Peptide-binding assays and HLA II transgenic Abeta degrees mice are consistent and complementary tools for identifying HLA II-restricted peptides.

The identification of MHC class II-restricted peptides has become a priority for the development of peptide-based prophylactic and therapeutic vaccines. The aim of this study was to assess the correlations between peptide-binding assays on purified HLA II molecules and immunization of human HLA II transgenic mice deficient in murine class II molecules (Abeta degrees ). We used as models two MHC class II-restricted peptides, one derived from the HIV Nef regulatory protein (Nef (56-68)) and the other from the Schistosoma mansoni 28-kDa glutathione-S-transferase (Sm28GST (190-211)). High correlations were found between the two approaches, which showed that the Nef (56-68) and Sm28GST (190-211) peptides may represent promiscuous ligands for HLA-DQ and for HLA-DR molecules, respectively. We suggest a rational method based on the combination of peptide-binding assays and HLA II transgenic mice experiments as consistent and complementary tools for selecting T helper epitopes.Journal Articleinfo:eu-repo/semantics/publishe

A dietary flavone confers communicable protection against colitis through NLRP6 signaling independently of inflammasome activation: Apigenin regulates bacterial ecology by Nlrp6 signaling

International audienceFlavones represent a class of polyphenols that are found in many plant-derived food sources. Herein, we provide evidence that the anti-inflammatory and antiproliferative effect of the flavone apigenin relies on the regulation of the gut microbiota by the NOD-like receptor family pyrin domain containing 6 (Nlrp6). When challenged by dextran sulfate sodium (DSS) in drinking water, mice were protected against colitis upon cohousing with apigenin-treated animals. In contrast, the protective effect was lost in the absence of Nlrp6. Sequencing of the 16S ribosomal RNA gene revealed a shift in the composition of the gut microbiota in apigenin-treated mice that was not observed in the absence of Nlrp6. Equally important, we find that the antiproliferative effect of apigenin was dominantly transmitted after cohousing, while being compromised in Nlrp6-deficient mice. In contrast, the symptoms of colitis were alleviated upon apigenin administration even in the absence of either caspase-1/11 or Asc. Collectively, these data indicate that apigenin modulated an inflammasome-independent mechanism by which Nlrp6 reprograms the gut microbiota for protecting mice against colitis. Our study highlights a modulation of the Nlrp6 signaling pathway by a prominent constituent of the human diet that may point toward improved ways to treat inflammatory bowel diseases

IL-7 modulates hypothalamic neuropeptide mRNA gene expression.

<p>PBS ( = 5, □) or IL-7 (n = 5, ▪) was i.p. injected in 2-month-old C57BL/6 mice. The expression of hypothalamic neuropeptides was assessed by real-time PCR, in fed (<b>A</b>) or in re-fed (<b>B</b>) condition. The effects of IL-7 treatment were evaluated by calculating the relative expression levels as follows: 2^ΔCt (ΔCt = mean Ct genes of interest - mean Ct GAPDH), using the raw cycle-threshold (Ct) values. *<i>p</i><0.05, *** <i>p</i><0.001. POMC: pro-opiomelanocortin, CART: cocaine-amphetamine related peptide, NP-Y: neuropeptide-Y, AgRP: Agouti-related peptide.</p