Adjuvants can be defined as pharmacological and immunological components that are able to modify and/or enhance antigen-specific immune responses. Based on the interdisciplinary research between immunology and material science/engineering, various vaccine adjuvant materials have been developed. By rational design and engineering of antigen or adjuvant materials, immune-modulatory vaccine systems generated to activate immune system. Here, we review the current progress of bioengineered prophylactic and/or therapeutic vaccine adjuvant for cancer and/or infectious disease, and discuss the prospect of future vaccine adjuvant materials.
Adjuvants, Immunologic ; Allergy and Immunology ; Communicable Diseases* ; Immune System ; Immunomodulation ; Immunotherapy*

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an intensive therapy to cure high-risk haematological malignant disorders, congenital diseases, autoimmune disease and so on. The main complication of HSCT is graft-versus-host disease (GVHD), which can cause the death of recipients and affect the therapeutic effect. Many kinds of immune cells and inflammatory factors were involved in the occurrence of GVHD. Twenty years ago the mice and human interleukin-17 (IL-17) were found. A new kind of T cell-CD4(+) IL-17(+) T was found in recent years, named Th17 cells. Now IL-17 and Th17 cells have become the hot spot in the research field of infection immunity, autoimmune diseases, tumor immunity and GVHD. In this article, immunoregulatory effects of interleukin-17 and Th17 cells in GVHD are reviewed.
Animals ; Graft vs Host Disease ; immunology ; therapy ; Humans ; Immunomodulation ; Interleukin-17 ; immunology ; Mice ; Th17 Cells ; immunology

Mesenchymal stem cells have generated great interest among researchers and physicians due to their unique biological characteristics and potential clinical applications. Here, I propose for the first time the concept of a hierarchical system which is composed of all mesenchymal stem cells from post-embryonic subtotipotent stem cells to MSC progenitors. Post-embryonic subtotipotent stem cells are left-over cells during embryonic development and are on the top of the hierarchy. MSC system is a combination of cells that are derived from different stages of embryonic development, possess different differentiation potential and ultimately give rise to cells that share a similar set of phenotypic markers. The concept of MSC system has important implications: (1) it entirely explains the three important biological characteristics of MSC: stem cell properties of MSC, MSC as components of tissue microenvironment and immunomodulatory functions of MSC. (2) It balances immune responses and tissue metabolism. (3) It could provide tissue-specific stem cells for clinical application with high efficiency and safety. In a word, this concept constitutes an important part of the biological properties of MSC and will help researchers gain better insight into MSC.
Cell Differentiation ; Cellular Microenvironment ; Humans ; Immunomodulation ; Mesenchymal Stromal Cells ; immunology ; physiology ; Phenotype

Sepsis is a systemic inflammatory response syndrome resulting from a host response to infection. The early stage of sepsis is characterized by excessive inflammatory response, accompanied by immune dysfunction characterized by aggravating cellular immunosuppression. The vast majority of patients with sepsis survive the initial excessive inflammatory response, but die of hospital-acquired infection, opportunistic pathogenic bacteria infection, latent virus reactivation, and multiple organ dysfunction syndrome. These facts indicate that immunosuppression may be a significant cause of exacerbation of the illness even death of the septic patients. The primary cellular mechanisms in inducing immune dysfunction include immune dysfunction of T lymphocytes, negative regulation of regulatory T lymphocytes and dendritic cells, and damage of intestinal mucosa associated lymphoid tissue. Xuebijing injection is a complex Chinese patent medicine, which is widely used in the treatment of sepsis. It has a potential immunoregulation ability, as well as effects on bacteriostasis, anti-endotoxin and anti-inflammation. Its target and mechanism of action need to be explored further.
Drugs, Chinese Herbal ; therapeutic use ; Humans ; Immunomodulation ; Sepsis ; drug therapy ; immunology

Mesenchymal stem cells (MSCs) are a kind of adult stem cells which have the capability to differentiate into multiple cell types as well as self-renew continuously. Recent studies demonstrate that MSCs are low immunogenic and able to exert immunomodulatory function by various approaches, such as suppression of the lymphocyte proliferation, reduction of the dentritic cell generation, maturation and function, down-regulation of the CTL formation and enhancement of regulatory T-cell proportion. In vivo experiments show that MSC infusion can prolong the survival time of allo-skin graft in baboon and ameliorate experimental autoimmune encephalomyelitis in mice. Successful reports have been documented about clinical application of MSC in the management of graft-versus-host disease. In this review, the immunological characteristics and the immunomodulation functions in vitro and in vivo of MSC were summarized.
Animals ; Graft vs Host Disease ; prevention & control ; Humans ; Immunomodulation ; physiology ; Mesenchymal Stromal Cells ; immunology ; physiology ; T-Lymphocytes, Regulatory ; immunology

We purified a novel mannose binding lectin form Musca domestica pupae by affinity chromatography on Con A-Sepharose 4B and DEAE weak anion-exchange chromatography. By SDS-PAGE, MBL-1 yielded a single band with the molecular weight of 24 kDa. It was a glycoprotein detected by periodic acid-schiffs staining reaction, with 97.36% protein and 2.1% oligosaccharide. Meanwhile, the results of beta-elimination reaction, infrared spectroscopy, atomic force microscopy and protein sequencing instrument show that MBL-1 was an ellipsoidal-shaped monomer with 60-100 nm in diameter. N-glycoside bond linked oligosaccharide chain and the N-terminal blocked peptide chain. Further study suggested that MBL-1 promote the proliferation of macrophage in a concentration-dependent manner. The scanning electron microscope analysis shows that MBL-1 promoted the activation of macrophages. These results show that MBL-1 purified from Musca domestica pupae possesses immune regulation effect, serving a reference basis to develop natural immune-modulator.
Animals ; Glycoproteins ; analysis ; Houseflies ; chemistry ; Immunomodulation ; immunology ; physiology ; Macrophages ; immunology ; Mannose-Binding Lectin ; chemistry ; physiology ; Oligosaccharides ; analysis ; Pupa ; chemistry

The role of alveolar macrophages (AMs) in the pathogenesis of asthma is still unknown. The aim of the present study was to investigate the effects of AM in the murine model of asthma. AMs were selectively depleted by liposomes containing clodronate just before allergen challenges, and changes in inflammatory cells and cytokine concentrations in bronchoalveolar lavage (BAL) fluid were measured. AMs were then adoptively transferred to AM-depleted sensitized mice and changes were measured. Phenotypic changes in AMs were evaluated after in vitro allergen stimulation. AM-depletion after sensitization significantly increased the number of eosinophils and lymphocytes and the concentrations of IL-4, IL-5 and GM-CSF in BAL fluid. These changes were significantly ameliorated only by adoptive transfer of unsensitized AMs, not by sensitized AMs. In addition, in vitro allergen stimulation of AMs resulted in their gaining the ability to produce inflammatory cytokines, such as IL-1beta, IL-6 and TNF-alpha, and losing the ability to suppress GM-CSF concentrations in BAL fluid. These findings suggested that AMs worked probably through GM-CSF-dependent mechanisms, although further confirmatory experiments are needed. Our results indicate that the role of AMs in the context of airway inflammation should be re-examined.
Animals ; Asthma/*immunology ; Bronchoalveolar Lavage Fluid/chemistry/cytology/immunology ; Cytokines/biosynthesis/immunology ; Disease Models, Animal ; Female ; Immunization ; Immunomodulation/*immunology ; Inflammation/*immunology ; Leukocytes/immunology ; Macrophages, Alveolar/*immunology ; Mice ; Mice, Inbred C57BL ; Ovalbumin/immunology

Sphingosine 1-phosphate (S1P) is an important biologically active lysophospholipid that transmits signals through a family of G-protein-coupled receptors (GPCRs) to regulate the vital functions of several types of immune cells. The S1P GPCRs suppress both generation of specialized functional cytokines, such as IFN-gamma and IL-4, and proliferation of T-cells. Although S1P is chemotactic to T cells, B cells, dendritic cells, and natural killer cells, the major effect of S1P on the immune system is the regulation of lymphocyte recirculation and tissue distribution by S1P and S1P1. Chemotactic response of CD4+CD25+ regulatory T cells to S1P is reduced, but its optimal suppressive activities require S1P. FTY720, a new class of immunomodulator, is rapidly phosphorylated by sphingosine kinase 2 in vivo to form the biologically active phosphorylated-FTY720 (FTY720-P), which closely resembles S1P. The FTY720-P is a true agonist for S1P1, S1P3, S1P4, and S1P5, it affects the tissue distribution and functional activity of T cells, B cells, dendritic cells and regulatory T cells. FTY720 were demonstrated to be a hypotoxic, great effective and reversible immunosuppressive efficacy to prevent allograft rejection and treat some autoimmune diseases. In this article, the synthesis and metabolism of S1P, the expression of S1P GPCRs in immune cells, the effect of S1P on immune cells, the drugs targeted to S1P GPCRs and their clinical implications are reviewed.
Fingolimod Hydrochloride ; Humans ; Immunomodulation ; physiology ; Lysophospholipids ; immunology ; physiology ; Propylene Glycols ; metabolism ; Receptors, G-Protein-Coupled ; immunology ; physiology ; Sphingosine ; analogs & derivatives ; immunology ; metabolism ; physiology

In the last 10 years, mesenchymal stem cells (MSCs) have emerged as a therapeutic approach to regenerative medicine, cancer, autoimmune diseases, and many more due to their potential to differentiate into various tissues, to repair damaged tissues and organs, and also for their immunomodulatory properties. Findings in vitro and in vivo have demonstrated immune regulatory function of MSCs and have facilitated their application in clinical trials, such as those of autoimmune diseases and chronic inflammatory diseases. There has been an increasing interest in the role of MSCs in allogeneic hematopoietic stem cell transplantation (HSCT), including hematopoietic stem cell engraftment and the prevention and treatment of graft-versus-host disease (GVHD), and their therapeutic potential has been reported in numerous clinical trials. Although the safety of clinical application of MSCs is established, further modifications to improve their efficacy are required. In this review, we summarize advances in the potential use of MSCs in HSCT. In addition, we discuss their use in clinical trials of the treatment of GVHD following HSCT, the immunomodulatory capacity of MSCs, and their regenerative and therapeutic potential in the field of HSCT.
Animals ; Chimerism ; Clinical Trials as Topic ; Graft vs Host Disease/immunology/therapy ; *Hematopoietic Stem Cell Transplantation ; Humans ; Immunomodulation ; Mesenchymal Stromal Cells/*cytology/immunology

OBJECTIVEThis study investigated the immunoregulatory and protective roles of Yinchenhao decoction, a compound of Chinese herbal medicine, in a mouse model of concanavalin A (ConA)-induced chronic liver injury.

METHODSFemale BalB/c mice were randomly divided into 4 groups: normal control, ConA model, ConA model treated with Yinchenhao decoction (400 mg/kg, orally), and ConA model treated with dexamethasone (0.5 mg/kg, orally). All treatments were given once a day for 28 d. Except of the normal control, mice received tail vein injection of ConA (10 mg/kg) on days 7, 14, 21, and 28, at 1 h after treatment with Yinchenhao decoction or dexamethasone or saline to induce chronic liver injury.

RESULTSRepeated ConA injection induced chronic liver injury, which was evidenced by inflammatory cell infiltration and necrosis, increased serum alanine aminotranferease activities, decreased albumin levels, and an imbalanced expression of immunoregulatory genes in the liver tissues including significantly enhanced interferon-γ, interleukin-4, monocyte chemotactic protein-1, and cluster of differentiation 163 mRNA levels, and reduced tumor necrosis factor-α and interleukin-6 mRNA levels. Treatment with Yinchenhao decoction significantly reversed the ConA-induced changes in immunoregulatory gene expression in the liver tissues, reduced serum alanine aminotranferease activity, enhanced serum albumin level, and attenuated the extent of liver inflammation and necrosis. Furthermore, Yinchenhao decoction did not result in hepatocyte degeneration and spleen weight loss that were observed in mice received long-term treatment with dexamethasone.

CONCLUSIONYinchenhao decoction treatment protected liver against the ConA-induced chronic liver damage and improved liver function, which were associated with the modulation of gene expression related to immune/inflammatory response.

Animals ; Chemical and Drug Induced Liver Injury, Chronic ; immunology ; prevention & control ; Concanavalin A ; toxicity ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Immunomodulation ; Mice ; Mice, Inbred BALB C