CYLD was originally identified as a tumor suppressor gene mutated in familial cylindromatosis, an autosomal dominant predisposition to multiple benign neoplasms of the skin known as cylindromas. The CYLD protein is a deubiquitinating enzyme that acts as a negative regulator of NF-κB and JNK signaling through its interaction with NEMO and TNFR-associated factor 2. We have previously described a novel mouse strain that expresses solely and excessively a naturally occurring splice variant of CYLD (CYLDex7/8). In this study, we demonstrate that CYLD plays a critical role in Treg development and function. T cells of CYLDex7/8 mice had a hyperactive phenotype manifested by increased production of inflammatory cytokines and constitutive activation of the NF-κB pathway. Furthermore, the amount of Foxp3+ regulatory T cells in these mice was markedly enhanced in thymus and peripheral organs. Importantly, these regulatory T cells displayed decreased expression levels of CD25 and CTLA-4 associated with impaired suppressive capacity. Hence, our data emphasize an essential role of CYLD in maintaining T cell homeostasis as well as normal T regulatory cell function, thereby controlling abnormal T cell responses.

PurposeCancer patients are at high risk of malnutrition and tumor cachexia further increasing morbidity and mortality. Reasons for cachexia are not clear yet, but inflammatory processes as well as the occurrence of taste disorders reducing nutrient uptake are discussed to play key roles. The purpose of this study was to gain insight into causative factors of taste disturbance in cancer patients. Does the cancer itself, inflammatory processes or cancer therapy influence taste disorders?MethodsTo capture an underlying taste disorder patients with cancer (n = 42), acutely hospitalized inflammatory disease patients (n = 57) and healthy controls (n = 39) were examined. To assess the influence of chemotherapy, patients with and without chemotherapy were compared. Taste tests were performed according to DIN ISO 3972:2011. Inflammation was recorded using laboratory parameters. Statistical evaluation was conducted using the Software R.ResultsCancer patients showed significantly increased taste thresholds for sweet, salty, and umami compared to healthy controls. There were no significant differences in taste detection and recognition between patients with former, current, or without chemotherapeutical treatment. Patients with an acute inflammatory disease showed an increased taste threshold for umami compared to healthy controls.ConclusionsIt could be shown that cancer patients suffer from taste disorders irrespective of an existing chemotherapeutical treatment. Cancer-related inflammation appears to have a greater impact on taste perception than an acute inflammatory process. Therefore, an adapted dietary adjustment should be carried out at an early stage for cancer patients in order to avoid nutritional disorders caused by a taste disorder.

Immunoglobulin heavy chain (IgH) class switch recombination and regulation of IgH expression levels are processes suggested to be controlled by the IgH 3′ enhancer. Here we demonstrate that CD40 or IgM receptor stimulation of primary B cells results in transactivation of this enhancer. 4‐Hydroxy‐3‐nitrophenylacetyl (NIP)‐BSA induction of a K46 B cell line expressing a chimeric NIP‐specific CD40 single chain receptor results in a ligand receptor‐dependent response of a 3′ enhancer ETS/AP‐1 minimal promoter construct. Gel retardation analysis and genomic footprinting experiments reveal that CD40 or IgM induction recruits NFAB (nuclear factors of activated B cells) to the ETS/AP‐1 motif. While IgM signalling recruits c‐Fos, JunB and Elf‐1 (NFAB‐I), only JunB and Elf‐1 were observed following CD40 signalling (NFAB‐II). CD40 signalling, however, induces a Fos family‐related partner for JunB, which may account for the transcriptional activity observed by NFAB‐II in K46 cells. We propose a model whereby CD40 and IgM receptor‐mediated signalling converge in the process of 3′ enhancer activation in B lymphocytes. Our data provide a putative molecular explanation as to why CD40L‐deficient mice, and possibly patients with hyper‐IgM syndrome, are unable to undergo T cell‐dependent class switch recombination but respond properly upon lipopolysaccharide‐induced switch recombination.

The MTT decreases in the first two hours after eating. The visually assessed and the software-based MTT correlate well, however MTT does not correlate with disease activity in patients with Crohn's disease.