Notes

Lumbosacral intraspinal extradural ganglion cyst within a cat.
[This corrects the article DOI 10.3389/fimmu.2020.00730.].Indoleamine-2,3-dioxygenase (IDO)1 and IDO2 are two closely related tryptophan catabolizing enzymes encoded by linked genes. The IDO pathway is also immunomodulatory, with IDO1 well-characterized as a mediator of tumor immune evasion. Due to its homology with IDO1, IDO2 has been proposed to have a similar immunoregulatory function. Indeed, IDO2, like IDO1, is necessary for the differentiation of regulatory T cells in vitro. However, compared to IDO1, in vivo studies demonstrated a contrasting role for IDO2, with experiments in preclinical models of autoimmune arthritis establishing a proinflammatory role for IDO2 in mediating B and T cell activation driving autoimmune disease. Given their potentially opposing roles in inflammatory responses, interpretation of results obtained using IDO1 or IDO2 single knockout mice could be complicated by the expression of the other enzyme. Here we use IDO1 and IDO2 single and double knockout (dko) mice to define the differential roles of IDO1 and IDO2 in B cell-mediated immune responses. Autoreactive T and B cell responses and severity of joint inflammation were decreased in IDO2 ko, but not IDO1 ko arthritic mice. Dko mice had a reduction in the number of autoantibody secreting cells and severity of arthritis however, percentages of differentiated T cells and their associated cytokines were not reduced compared to IDO1 ko or wild-type mice. These data suggest that autoreactive B cell responses are mediated by IDO2, while autoreactive T cell responses are indirectly affected by IDO1 expression in the IDO2 ko mice. IDO2 also influenced antibody responses in models of influenza infection and immunization with T cell-independent type II antigens. Taken together, these studies provide evidence for the contrasting roles IDO1 and IDO2 play in immune responses, with IDO1 mediating T cell suppressive effects and IDO2 working directly in B cells as a proinflammatory mediator of B cell responses.[This corrects the article DOI 10.3389/fimmu.2018.01091.].Vibriosis is a commonly found bacterial disease identified among fish and shellfish cultured in saline waters. A multitude of Vibrio species have been identified as the causative agents. LamB, a member of outer membrane protein (OMPs) family of these bacteria is conserved among all Vibrio species and has been identified as an efficient vaccine candidate against vibriosis. Rootless duckweed (Wolffia) is a tiny, edible aquatic plant possessing characteristics suitable for the utilization as a bioreactor. Thus, we attempted to express a protective edible vaccine antigen against fish vibriosis in nuclear-transformed Wolffia. We amplified LamB gene from virulent Vibrio alginolyticus and it was modified to maximize the protein expression level and translocate the protein to the endoplasmic reticulum (ER) in plants. It was cloned into binary vector pMYC under the control of CaMV 35S promoter and introduced into Wolffia globosa by Agrobacterium-mediated transformation. Integration and expression of the LamB gene was confirmed by genomic PCR and RT-PCR. Western blot analysis revealed accumulation of the LamB protein in 8 transgenic lines. The cross-protective property of transgenic Wolffia was evaluated by orally vaccinating zebrafish through feeding fresh transgenic Wolffia and subsequently challenging with virulent V. alginolyticus. High relative percent survival (RPS) of the vaccinated fish (63.3%) confirmed that fish immunized with transgenic Wolffia were well-protected from Vibrio infection. These findings suggest that Wolffia expressed LamB could serve as an edible plant-based candidate vaccine model for fish vibriosis and feasibility of utilizing Wolffia as bioreactor to produce edible vaccines.Protein tyrosine phosphatase non-receptor type 2 (PTPN2) plays a pivotal role in immune homeostasis and has been associated with human autoimmune and chronic inflammatory diseases. Though PTPN2 is well-characterized in lymphocytes, little is known about its function in innate immune cells. Our findings demonstrate that dendritic cell (DC)-intrinsic PTPN2 might be the key to explain the central role for PTPN2 in the immune system to maintain immune tolerance. Partial genetic PTPN2 ablation in DCs resulted in spontaneous inflammation, particularly in skin, liver, lung and kidney 22 weeks post-birth. DC-specific PTPN2 controls steady-state immune cell composition and even incomplete PTPN2 deficiency in DCs resulted in enhanced organ infiltration of conventional type 2 DCs, accompanied by expansion of IFNγ-producing effector T-cells. Consequently, the phenotypic effects of DC-specific PTPN2 deficiency were abolished in T-cell deficient Rag knock-out mice. Our data add substantial knowledge about the molecular mechanisms to prevent inflammation and maintain tissue tolerance.Current treatments for chronic immune-mediated diseases such as psoriasis, rheumatoid arthritis, or Crohn's disease commonly rely on cytokine neutralization using monoclonal antibodies; however, such approaches have drawbacks. Frequent repeated dosing can lead to the formation of anti-drug antibodies and patient compliance issues, and it is difficult to identify a single antibody that is broadly efficacious across diverse patient populations. As an alternative to monoclonal antibody therapy, anti-cytokine immunization is a potential means for long-term therapeutic control of chronic inflammatory diseases. Here we report a supramolecular peptide-based approach for raising antibodies against IL-17 and demonstrate its efficacy in a murine model of psoriasis. B-cell epitopes from IL-17 were co-assembled with the universal T-cell epitope PADRE using the Q11 self-assembling peptide nanofiber system. These materials, with or without adjuvants, raised antibody responses against IL-17. Exploiting the modularity of the system, multifactorial experimental designs were used to select formulations maximizing titer and avidity. In a mouse model of psoriasis induced by imiquimod, unadjuvanted nanofibers had therapeutic efficacy, which could be enhanced with alum adjuvant but reversed with CpG adjuvant. Measurements of antibody subclass induced by adjuvanted and unadjuvanted formulations revealed strong correlations between therapeutic efficacy and titers of IgG1 (improved efficacy) or IgG2b (worsened efficacy). this website These findings have important implications for the development of anti-cytokine active immunotherapies and suggest that immune phenotype is an important metric for eliciting therapeutic anti-cytokine antibody responses.
My Website: https://www.selleckchem.com/products/azd2014.html