Generation Of Immune Tolerance Research Articles

Establishment of local allergic rhinitis tolerance in mouse model

Objective:To establish a mouse model of local allergic rhinitis tolerance by intranasal infusion of allergen, and study its immunological indexes and characteristics. Methods:The mice were given ovalbumin（OVA） and phosphate buffer solution（PBS） daily, and their allergic symptoms were recorded. OVA-specific antibodies（IgE, IgG1, IgG2a） in serum and cytokine（IL-4, IL-10, IFN-γ） in splenic culture supernatant were detected. The infiltration of eosinophils and goblet cells in nasal mucosa were observed, and the changes in local nasal mucosa genes were analyzed by RNA-seq technique. Results:Mice first showed aggravation of allergic symptoms when stimulated with OVA. The serum OVA-specific antibodies IgE, IgG1, IgG2a and the cytokine（IL-4, IL-10, IFN-γ） Iin splenic culture supernatant were increased, the eosinophils and goblet cells in nasal mucosa were significantly increased. The expression of encoding IL-10, TGF-β gene and eosinophils activation gene in nasal mucosa were up-regulated. As the duration of nasal dripping increased, the allergic symptoms gradually decreased, serum OVA-specific antibodies IgE, IgG1, IgG2a continued to increase. Splenic culture supernatant IL-4 decreased, IL-10 increased, IFN-γ had a downward trend. In nasal mucosa, goblet cells decreased significantly. Genes involved in eosinophils activation were significantly down-regulated. The encoding tolerance genes such as IL-10 and TGF-β genes remained highly expressed. Ten core genes associated with immune tolerance in localized allergic rhinitis were screened, Rps27a, Uba52, Kng2, Gnal, C3, Rtp4, Reep1, Rtp2, Rtp1, Reep5. Conclusion:The mice first develop an allergy and then develop immune tolerance by continuous local drops of the allergen. The generation of immune tolerance may be induced by the continuous action of allergens, which induced systemic and local immune tolerance effects.

Advances and challenges of immunocheckpoint inhibitors in the treatment of primary liver cancer.

Primary liver cancer (PLC) is one of the most common malignant tumors, which clinically characterized by occult onset, rapid development, easy recurrence and poor prognosis. With the rapid development of tumor immunotherapy research, tumor immunotherapy has also achieved remarkable clinical efficacy, and jointly promoted the overall improvement of tumor immunology from mechanism research to clinical transformation, from single discipline to multi-disciplinary integration. Immunotherapy has obvious advantages in treatment-related toxicity and efficacy compared with traditional therapy. In hepatocellular carcinoma (HCC), immunotherapy alone or in combination with other therapies may help to control tumor progression, and there are many immune checkpoint inhibitors (ICIs) widely used in clinical or ongoing clinical trials. However, tumor immunology research is still facing many challenges. How to effectively evaluate the efficacy, whether there are related biomarkers, the generation of immune tolerance and the lack of clinical trials to objectively evaluate the efficacy are still urgent problems to be solved, but it also brings new research opportunities for basic and clinical immunology researchers. The study of treatment of ICIs of PLC has become a hot spot in clinical research field. This paper summarizes and prospects the research progress and challenges of ICIs for PLC.

A narrative review of in utero gene therapy: advances, challenges, and future considerations.

The field of in utero gene therapy (IUGT) represents a crossroad of technologic advancements and medical ethical boundaries. Several strategies have been developed for IUGT focusing on either modifying endogenous genes, replacing missing genes, or modifying gene transcription products. The list of candidate diseases such as hemoglobinopathies, cystic fibrosis, lysosomal storage disorders continues to grow with new strategies being developed as our understanding of their respective underlying molecular pathogenesis increases. Treatment in utero has several distinct advantages to postnatal treatment. Biologic and physiologic phenomena enable the delivery of a higher effective dose, generation of immune tolerance, and the prevention of phenotypic onset for genetic diseases. Therapeutic technology for IUGT including CRISPR-Cas9 systems, zinc finger nucleases (ZFN), and peptide nucleic acids (PNAs) has already shown promise in animal models and early postnatal clinical trials. While the ability to detect fetal diagnoses has dramatically improved with developments in ultrasound and next-generation sequencing, treatment options remain experimental, with several translational gaps remaining prior to implementation in the clinical realm. Complicating this issue, the potential diseases targeted by this approach are often debilitating and would otherwise prove fatal if not treated in some manner. The leap from small animals to large animals, and subsequently, to humans will require further vigorous testing of safety and efficacy.

The role of microRNA miR223 in immune adaptation for pregnancy and fetal-placental development

The role of microRNA miR223 in immune adaptation for pregnancy and fetal-placental development

The prospect of pluripotent stem cell-based therapy

Human embrional stem cells (hESC) are able to maintain pluripotency in culture, to proliferate indefinitely and to differentiate into any somatic cell type. Due to these unique properties, hESC may become an exceptional source of tissues for transplantation and have great potential for the therapy of incurable diseases. Here, we review new developments in the area of embrional stem cells and discuss major challenges--standartization of protocols for cell derivation and cultivation, identification of specific molecular markers, development of new aprouches for directed differentiation etc.--which remain to be settled, prior to safe and successful clinical application of stem cells. We appraise several potential approaches of hESC therapy including derivation of autologous cells via therapeutic cloning (1), generation of immune tolerance to allogenic donor cells via hematopoetic chimerism (2), and development of the banks of hESC lines (3). In addition, we discuss brifly induced pluripotent cells, which are derived via genetic modification of autologous somatic cells and are analogous to ESC. Our analysis demonstrates that uncontrollable differentiation in vivo and teratogenic potential of hESC are critical limitations of their application in clinic. Therefore, the major direction of hESC use is derivation of a specific differentiated progeny, which has lower proliferative potential and immune privilege, yet poses fewer risks. Finally, cell therapy is far more complex and resource-consuming process as compared to drug-based medicine; pluripotent stem cell biology and technology is in need of further investigation and development before these cells can be used in clinics.

Fas Ligand as a Tool for Immunosuppression and Generation of Immune Tolerance

The role of Fas ligand (FasL) in physiologically limiting immune responses and maintaining immune-privileged sites has led to a body of research aiming to confer protection to allogeneic grafts by expressing FasL on the allogeneic tissue or by administrating FasL-transduced donor dendritic cells. In addition, several studies have used FasL to abrogate autoimmune responses. This review presents the results of these studies and discusses the problems associated with FasL usage.