Donahuetorres4479

Experimental autoimmune uveitis (EAU) is a CD4+ T cell-mediated organ-specific autoimmune disease and has been considered as a model of human autoimmune uveitis. Dracocephalum heterophyllum (DH) is a Chinese herbal medicine used in treating hepatitis. DH suppressed the production of inflammatory cytokines through the recruitment of myeloid-derived suppressor cells (MDSCs) to the liver. However, it remains elusive whether DH can directly regulate CD4+ T cell biology and hence ameliorates the development of CD4+ T cell-mediated autoimmune disease. In the current study, we found that DH extract significantly suppressed the production of pro-inflammatory cytokines by CD4+ T cells. Further study showed that DH didn't affect the activation, differentiation, and apoptosis of CD4+ T cells. Instead, it significantly suppressed the proliferation of conventional CD4+ T cells both in vitro and in vivo. Mechanistic study showed that DH-treated CD4+ T cells were partially arrested at the G2/M phase of the cell cycle because of the enhanced inhibitory phosphorylation of Cdc2 (Tyr15). In addition, we demonstrated that treatment with DH significantly ameliorated EAU in mice through suppressing the proliferation of autoreactive antigen specific CD4+ T cells. Taken together, the current study indicates that DH-mediated suppression of CD4+ T cell proliferation may provide a promising therapeutic strategy for treating CD4+ T cell-mediated diseases.Autoimmune hepatitis (AIH) is a severe and chronic liver disease, and its incidence has increased worldwide in recent years. Research into the pathogenesis of AIH remains limited largely owing to the lack of suitable mouse models. The concanavalin A (ConA) mouse model is a typical and well-established model used to investigate T cell-dependent liver injury. However, ConA-induced hepatitis is acute and usually disappears after 48 h; thus, it does not mimic the pathogenesis of AIH in the human body. Several studies have explored various AIH mouse models, but as yet there is no widely accepted and valid mouse model for AIH. Immunosuppression is the standard clinical therapy for AIH, but patient side effects and recurrence limit its use. Regulatory T cells (Tregs) play critical roles in the maintenance of immune homeostasis and in the prevention of autoimmune diseases, which may provide a potential therapeutic target for AIH therapy. However, the role of Tregs in AIH has not yet been clarified, partly because of difficulties in diagnosing AIH and in collecting patient samples. In this review, we discuss the studies related to Treg in various AIH mouse models and patients with AIH and provide some novel insights for this research area.Bacillus Calmette-Guerin (BCG) is the only licensed vaccine to prevent children from tuberculosis (TB), whereas it cannot provide effective protection for adults. Our previous work showed a novel vaccine candidate, liposomal adjuvant DMT emulsified with a multistage antigen CMFO, could protect mice against primary progressive TB, latency, and reactivation. To develop a more effective vaccine against adult TB, we aimed to further understand the role of pattern recognition receptor (PRR) agonists monophosphoryl lipid A (MPLA) and trehalose-6,6'-dibehenate (TDB) of the liposomal adjuvant DMT in the CMFO subunit vaccine-induced protection. Using C57BL/6 mouse models, the current study prepared different dimethyldioctadecylammonium (DDA)-based liposomal adjuvants with MPLA, TDB, or both (DMT), and then compared the immunogenicity and the protective efficacy among different liposomal adjuvanted CMFO subunit vaccines. Our study demonstrated that CMFO/DMT provided stronger and longer-lasting protective efficacy than the CMFO emulsified with adjuvants DDA or DDA/TDB. In addition, DDA/MPLA adjuvanted CMFO conferred a comparable protection in the lung as CMFO/DMT did. Higher levels of IFN-γ, IL-2, TNF-α, and IL-17A secreted by splenocytes were related with a more powerful and durable protection induced by CMFO/DMT through a putative synergistic effect of both MPLA and TDB via binding to TLR4 and Mincle. IL-2+ CD4+ T cells, especially IL-2+ CD4+ TCM cells, in the lung after infection were significantly associated with the vaccine-induced protection, whereas stronger IL-10 response and lower IL-2+ CD4+ T cells also contributed to the inferior protection of the DDA/TDB adjuvanted CMFO subunit vaccine. Given their crucial roles in vaccine-induced protection, combinational different PRR agonists in adjuvant formulation represent a promising strategy for the development of next-generation TB vaccine.Mesenchymal stromal cells (MSC) have been used in over 800 clinical trials with encouraging results in the field of transplant medicine and chronic inflammatory diseases. Pyrotinib nmr Today, Umbilical Cord (UC)-derived MSC are the second leading source used for clinical purposes, mainly due to its easy access and superior immune modulatory effects. Although the underlying molecular mechanisms of immune suppressive activities have not been fully understood, research over the last decade strongly suggests that MSC-mediated benefits are closely related to activation of secretome networks. Nevertheless, recent findings also point to cytokine-independent mechanisms as key players of MSC-mediated immune modulation. Here, we set up a robust in vitro immune assay using phytohemagglutinin- or anti-CD3/CD28-treated human peripheral blood mononuclear cells in cell-to-cell interaction or in cell-contact independent format with UC-MSC and conducted integrated transcriptome and secretome analyses to dissect molecular pathways driving UC-MSC-mediated immune modulation. Under inflammatory stimuli, multiparametric analyses of the secretome led us to identify cytokine/chemokine expression patterns associated with the induction of MSC-reprogrammed macrophages and T cell subsets ultimately leading to immune suppression. UC-MSC transcriptome analysis under inflammatory challenge allowed the identification of 47 differentially expressed genes, including chemokines, anti- and pro-inflammatory cytokines and adhesion molecules found also in UC-MSC-immunosupressive secretomes, including the novel candidate soluble IL-2R. This study enabled us to track functionally activated UC-MSC during immune suppression and opened an opportunity to explore new pathways involved in immunity control by UC-MSC. We propose that identified immunomodulatory molecules and pathways could potentially be translated into clinical settings in order to improve UC-MSC-therapy quality and efficacy.