Tolerogenic Dendritic Cells Generated with Tofacitinib Ameliorate Experimental Autoimmune Encephalomyelitis through Modulation of Th17/Treg Balance

It is well known that dendritic cells (DCs) play a pivotal role in triggering self-specific responses. Conversely, tolerogenic DCs (tolDCs), a specialized subset, induce tolerance and negatively regulate autoreactive responses. Tofacitinib, a Janus kinase inhibitor developed by Pfizer for treatment of rheumatoid arthritis, is probable to be a promising candidate for inducing tolDCs. The aims of this study were to evaluate the effectiveness of tolDCs induced by tofacitinib in a myelin oligodendrocyte glycoprotein- (MOG-) specific experimental autoimmune encephalomyelitis (EAE) model and to investigate their effects on Th17/Treg balance in the animal model of multiple sclerosis (MS). Our results revealed that tofacitinib-treated DCs maintained a steady semimature phenotype with a low level of proinflammatory cytokines and costimulatory molecules. DCs treated by tofacitinib also induced antigen-specific T cells hyporesponsiveness in a concentration-dependent manner. Upon intravenous injection into EAE mice, MOG pulsed tolDCs significantly dampened disease activity, and adoptive cell therapy (ACT) disturbed Th17/Treg balance with a remarkable decrease of Th1/Th17 cells and an increase in regulatory T cells (Tregs). Overall, DCs modified by tofacitinib exhibited a typical tolerogenic phenotype, and the antigen-specific tolDCs may represent a new avenue of research for the development of future clinical treatments for MS

Additional file 1 of Overexpression of PtoMYB115 improves lignocellulose recalcitrance to enhance biomass digestibility and bioethanol yield by specifically regulating lignin biosynthesis in transgenic poplar

Additional file 1: Table S1. Gene primers used in this study. Figure S1. Measurement of plant growth and gene expression in transgenic poplar plants. (a) Images of 3-month-old transgenic poplar lines and wild type (WT); Scale bar as 10 cm. (b) Expression of cell differentiation genes in PtoMYB115 transgenic plants and WT. Primers are listed in Table S1. The poplar ubiquitin gene was used as an internal control. All data are given as means ± SD from three biological repeats. Statistical analyses were performed using Student’s t test as **P < 0.01 (n = 3). Figure S2. Observations of plant cell wall formation in the PtoMYB115 transgenic lines and WT. (a) Cell wall thickness of SEM observation; (b) Cellulose and hemicellulose contents (% biomass). All data as means ± SD. Student’s t-test was performed between the transgenic line and WT as **P < 0.01 (n = 3). Figure S3. Comparison of lignocellulose features between the transgenic lines and WT. (a) Crystalline index (CrI) of crude cellulose. (b) Correlation analysis between lignocellulose features and hexose yields (% biomass) released from enzymatic hydrolyses after H2SO4 or CaO pretreatment. **Significant correlation at P < 0.01 (n = 15). Figure S4. Correlation analysis between DP of cellulose and hexose yields (% biomass) released from enzymatic hydrolyses after pretreatments. Figure S5. Quantitative RT-PCR analysis of proanthocyanidin biosynthetic genes in the PtoMYB115 transgenic lines and WT

DataSheet_1_Efficacy of Pgp3 vaccination for Chlamydia urogenital tract infection depends on its native conformation.pdf

Urogenital tract infections with Chlamydia trachomatis have frequently been detected among patients diagnosed with sexually transmitted infections, and such infections lead to inflammatory complications. Currently, no licensed chlamydial vaccine is available in clinical practice. We previously reported that immunization with recombinant C. trachomatis plasmid-encoded virulence factor Pgp3 provided cross-serovar protection against C. muridarum genital tract infection. Because Pgp3 is a homotrimer and human antisera only recognize the trimeric form of Pgp3, we compared the effects of the native conformation of Pgp3 (trimer) and heat-denatured Pgp3 (monomer) to determine whether the native conformation is dispensable for the induction of protective immunity against chlamydial vaginal challenge. Both Pgp3 trimer and monomer immunization induced corresponding specific antibody production, but only trimer-induced antibody recognized endogenous Pgp3, and trimer-immunized mouse splenocytes showed the highest IFN-γ production upon restimulation with the chlamydial elementary body or native Pgp3 in vitro. Importantly, only Pgp3 trimer-immunized mice showed shortened lower genital tract chlamydial shedding and decreased upper genital tract pathology. Thus, Pgp3-induced protective immunity against Chlamydia urogenital tract infection is highly dependent on the native conformation, which will guide the design of Pgp3-based polypeptides and multi-subunit chlamydial vaccines.</p