Intracellular Galectin-9 Enhances Proximal TCR Signaling and Potentiates Autoimmune Diseases.

Galectin-9 is a risk gene in inflammatory bowel disease. By transcriptomic analyses of ileal biopsies and PBMCs from inflammatory bowel disease patients, we identified a positive correlation between galectin-9 expression and colitis severity. We observed that galectin-9-deficient T cells were less able to induce T cell-mediated colitis.

SUMO-defective c-Maf preferentially transactivates Il21 to exacerbate autoimmune diabetes.

SUMOylation is involved in the development of several inflammatory diseases, but the physiological significance of SUMO-modulated c-Maf in autoimmune diabetes is not completely understood. Here, we report that an age-dependent attenuation of c-Maf SUMOylation in CD4+ T cells is positively correlated with the IL-21-mediated diabetogenesis in NOD mice. Using 2 strains of T cell-specific transgenic NOD mice overexpressing wild-type c-Maf (Tg-WTc) or SUMOylation site-mutated c-Maf (Tg-KRc), we demonstrated that Tg-KRc mice developed diabetes more rapidly than Tg-WTc mice in a CD4+ T cell-autonomous manner.

Peripheral Autoimmune Regulator Induces Exhaustion of CD4 and CD8 Effector T Cells to Attenuate Autoimmune Diabetes in Non-Obese Diabetic Mice.

Autoimmune regulator () is one of the most crucial genes expressed in the thymus, where it orchestrates the promiscuous expression and presentation of tissue-specific antigens during thymocyte selection. The presence of Aire-expressing cells outside the thymus points toward its plausible extrathymic functions; however, the relative contribution of Aire-expressing cells of hematopoietic origin and their role in the modulation of autoimmune diseases are still obscure. Here, we report that non-obese diabetic mice with transgenic Aire expression under the control of the CD11c (integrin alpha X) promoter were significantly protected from autoimmune diabetes compared with their non-transgenic littermates.

New insights into Blimp-1 in T lymphocytes: a divergent regulator of cell destiny and effector function.

B lymphocyte-induced maturation protein-1 (Blimp-1) serves as a master regulator of the development and function of antibody-producing B cells. Given that its function in T lymphocytes has been identified within the past decade, we review recent findings with emphasis on its role in coordinated control of gene expression during the development, differentiation, and function of T cells. Expression of Blimp-1 is mainly confined to activated T cells and is essential for the production of interleukin (IL)-10 by a subset of forkhead box (Fox)p3 regulatory T cells with an effector phenotype.

Targeting tumour necrosis factor receptor 1 assembly reverses Th17-mediated colitis through boosting a Th2 response.

Objective: The soluble preligand assembly domain (PLAD) of tumour necrosis factor receptor 1 (TNFR1) interferes with receptor trimerisation to block downstream signalling, and mediates Th17 suppression. We explored the therapeutic potential of recombinant PLAD.Fc protein on a spontaneous experimental colitis.

T cell-specific BLIMP-1 deficiency exacerbates experimental autoimmune encephalomyelitis in nonobese diabetic mice by increasing Th1 and Th17 cells.

Recently, we demonstrated that B lymphocyte-induced maturation protein 1 (BLIMP-1) has a role in regulating the differentiation and effector function of Th1 and Th17 cells. As these cells play critical roles in the induction and pathogenesis of experimental autoimmune encephalomyelitis (EAE), we investigated the potential role of T cell BLIMP-1 in modulating MOG35-55-induced EAE. We established T cell-specific BLIMP-1 conditional knockout (CKO) NOD mice to dissect the role of BLIMP-1 in EAE using loss-of-function model.

Downregulation of miR-29 contributes to cisplatin resistance of ovarian cancer cells.

Drug resistance is an obstacle to the treatment of ovarian cancer. Using a unique cell model, we have proven previously that a subpopulation of ovarian cancer cells is more resistant to cisplatin than are the original cells. MicroRNAs (miRNAs), small noncoding RNAs, are involved in many biological events in cancer cells.

Different modulation of Ptpn22 in effector and regulatory T cells leads to attenuation of autoimmune diabetes in transgenic nonobese diabetic mice.

Ptpn22 encodes PEST domain-enriched tyrosine phosphatase (Pep), which negatively regulates TCR proximal signaling and is strongly associated with a variety of autoimmune diseases in humans. The net effect of Pep on the balance of immunity and tolerance is uncertain because of the simultaneous inhibition of TCR-mediated signaling of effector and regulatory T cells (T(regs)). In this study, we generated transgenic NOD mice that overexpressed Pep in T cells.

Tyrosine phosphorylation of c-Maf enhances the expression of IL-4 gene.

Maf proteins are involved in a variety of biological processes, such as oncogenesis, lens development, and differentiation. In immune system, c-Maf transactivates IL-4 promoter, and ectopic expression of c-Maf skews primary T cell response toward the Th2 pathway. Numerous transcription factors are subjected to posttranslational modification.

A noncontact footpad thickness assay to evaluate rheumatoid disease.

Measuring soft tissue thickness is an important step in rheumatoid disease research. The severity of mouse footpad swelling can be used as an indicator of disease progression. A noncontact footpad thickness assay, simplified geometry measurement system (SGMS), was developed that was able to reduce both intra- and interobserver variances during measurements.

IL-1beta in irrigation fluid and mRNA expression in synovial tissue of the knee joint as therapeutic markers of inflammation in collagen antibody-induced arthritis.

Objective: We studied the relationship between the severity of inflammation and IL-1beta production and relative expression level of IL-1beta mRNA in irrigation fluid and synovial tissue obtained from the knee joint during the acute stage of a murine model of type II collagen antibody-induced arthritis (CAIA). This model is used to identify potential therapeutic markers for treating rheumatoid arthritis.

Methods: Irrigation fluid and synovium tissue were harvested from the knee joint of BALB/c mice in acute stage of CAIA induction.

Effect of exposure to long photoperiod during the rearing period on the age at first egg and the subsequent reproductive performance in geese.

The objective of this study was to investigate the effects of photoperiods longer than 14 h of light:10 h of dark (14L:10D) during the rearing period on the age at first egg laying (AFE) and the subsequent reproductive performance in geese. Sixty-six White Roman geese (18 male and 48 female) were divided into three groups and subjected to different lighting schemes, i.e.