USP28 protects development of inflammation in mouse intestine by regulating STAT5 phosphorylation and IL22 production in T lymphocytes.

Introduction: Ubiquitin-specific proteases (USPs), a large subset of more than 50 deubiquitinase proteins, have recently emerged as promising targets in cancer. However, their role in immune cell regulation, particularly in T cell activation, differentiation, and effector functions, remains largely unexplored.

Methods: We utilized a USP28 knockout mouse line to study the effect of USP28 on T cell activation and function, and its role in intestinal inflammation using the dextran sulfate sodium (DSS)-induced colitis model and a series of in vitro assays.

Absence of NC14A Domain of COLXVII/BP180 in Mice Results in IL-17‒Associated Skin Inflammation.

The deletion of exon 18 from Col17a1 in transgenic ΔNC14A mice results in the absence of the NC14A domain. NC14A corresponds to the human NC16A domain, the immunodominant epitope in bullous pemphigoid. Before the age of 1 year, 84% of ΔNC14A mice have developed severe itch and skin erosion.

The effects of post-translational modifications on Th17/Treg cell differentiation.

Regulatory T (Treg) cells and Th17 cells are subsets of CD4 T cells which play an essential role in immune homeostasis and infection. Dysregulation of the Th17/Treg cell balance was shown to be implicated in the development and progression of several disorders such as autoimmune disease, inflammatory disease, and cancer. Multiple factors, including T cell receptor (TCR) signals, cytokines, metabolic and epigenetic regulators can influence the differentiation of Th17 and Treg cells and affect their balance.

Gene Doping with Peroxisome-Proliferator-Activated Receptor Beta/Delta Agonists Alters Immunity but Exercise Training Mitigates the Detection of Effects in Blood Samples.

Synthetic ligands of peroxisome-proliferator-activated receptor beta/delta (PPARβ/δ) are being used as performance-enhancing drugs by athletes. Since we previously showed that PPARβ/δ activation affects T cell biology, we wanted to investigate whether a specific blood T cell signature could be employed as a method to detect the use of PPARβ/δ agonists. We analyzed in primary human T cells the in vitro effect of PPARβ/δ activation on fatty acid oxidation (FAO) and on their differentiation into regulatory T cells (Tregs).

Invalidation of the Transcriptional Modulator of Lipid Metabolism PPARβ/δ in T Cells Prevents Age-Related Alteration of Body Composition and Loss of Endurance Capacity.

Anti-inflammatory regulatory T cells (Tregs) are the most metabolically flexible CD4 T cells by using both glycolysis and fatty acid oxidation (FAO) which allow them to migrate in tissues. With aging, Tregs accumulate in secondary lymphoid organs and are involved in impairment of skeletal muscle (SKM) regeneration and mass maintenance. In this study, we showed that a deletion of a FAO modulator, peroxisome proliferator-activated receptor beta/delta (PPARβ/δ), specifically in T cells (KO-T PPARβ/δ), increased the number of CD4 T cells at day 2 following a cardiotoxin-induced SKM regeneration.

Complementary Immunometabolic Effects of Exercise and PPARβ/δ Agonist in the Context of Diet-Induced Weight Loss in Obese Female Mice.

Regular aerobic exercise, independently of weight loss, improves metabolic and anti-inflammatory states, and can be regarded as beneficial in counteracting obesity-induced low-grade inflammation. However, it is still unknown how exercise alters immunometabolism in a context of dietary changes. Agonists of the Peroxisome Proliferator Activated-Receptor beta/delta (PPARβ/δ) have been studied this last decade as "exercise-mimetics", which are potential therapies for metabolic diseases.

Developmental Requirement of Homeoprotein Otx2 for Specific Habenulo-Interpeduncular Subcircuits.

The habenulo-interpeduncular system (HIPS) is now recognized as a critical circuit modulating aversion, reward, and social behavior. There is evidence that dysfunction of this circuit leads to psychiatric disorders. Because psychiatric diseases may originate in developmental abnormalities, it is crucial to investigate the developmental mechanisms controlling the formation of the HIPS.

Decrease in αβ/γδ T-cell ratio is accompanied by a reduction in high-fat diet-induced weight gain, insulin resistance, and inflammation.

The implication of αβ and γδ T cells in obesity-associated inflammation and insulin resistance (IR) remains uncertain. Mice lacking γδ T cells show either no difference or a decrease in high-fat diet (HFD)-induced IR, whereas partial depletion in γδ T cells does not protect from HFD-induced IR. αβ T-cell deficiency leads to a decrease in white adipose tissue (WAT) inflammation and IR without weight change, but partial depletion of these cells has not been studied.

Regulation of Immune Cell Function by PPARs and the Connection with Metabolic and Neurodegenerative Diseases.

Increasing evidence points towards the existence of a bidirectional interconnection between metabolic disease and neurodegenerative disorders, in which inflammation is linking both together. Activation of members of the peroxisome proliferator-activated receptor (PPAR) family has been shown to have beneficial effects in these interlinked pathologies, and these improvements are often attributed to anti-inflammatory effects of PPAR activation. In this review, we summarize the role of PPARs in immune cell function, with a focus on macrophages and T cells, and how this was shown to contribute to obesity-associated inflammation and insulin resistance, atherosclerosis, and neurodegenerative disorders.

A role for Peroxisome Proliferator-Activated Receptor Beta in T cell development.

Metabolism plays an important role in T cell biology and changes in metabolism drive T cell differentiation and fate. Most research on the role of metabolism in T lymphocytes focuses on mature T cells while only few studies have investigated the role of metabolism in T cell development. In this study, we report that activation or overexpression of the transcription factor Peroxisome Proliferator-Activated Receptor β (PPARβ) increases fatty acid oxidation in T cells.