The immune system maintains the integrity of our bodies by warding off intruding microorganisms, but by sustaining tolerance to our own tissues. The immunologic tolerance is established by several layers of safeguards, including physical elimination of self-reactive lymphocytes during their development in the central lymphoid organs, anergy induction in autoreactive lymphocytes before their emigration to the periphery, or production regulatory T lymphocytes that suppress the activation, proliferation, and differentiation of various effector cells. The major regulatory T lymphocytes display their phenotype as CD4(+)CD25(+)Foxp3(+) and constitute about 10% of the peripheral T lymphocytes. Even with these safeguards, the immunologic tolerance sometimes fails and generates autoimmune diseases. Scientists studying the pathogenesis of autoimmune diseases pay particular attention to a CD4(+) T lymphocytes subset, Th17 lymphocytes, distinct from Th1 and Th2. Th17 produces diverse proinflammatory cytokines including IL-17 and TNF-alpha. Th17 and these cytokines are causatively associated with many episodes of autoimmune diseases. Accumulated data reveal the critical role of Th17 cells in the pathology of autoimmunity and portray them as an important target in the treatment of various autoimmune diseases. In this article, we will describe the main characteristics of regulatory T cells and Th17 cells and their cellular and molecular mechanisms of protective or destructive functions, respectively.
Autoimmune Diseases ; Autoimmunity ; Cytokines ; Emigration and Immigration ; Immune System ; Interleukin-17 ; Lymphocytes ; Phenotype ; T-Lymphocytes ; T-Lymphocytes, Regulatory ; Th17 Cells ; Tumor Necrosis Factor-alpha

The immune system maintains the integrity of our bodies by warding off intruding microorganisms, but by sustaining tolerance to our own tissues. The immunologic tolerance is established by several layers of safeguards, including physical elimination of self-reactive lymphocytes during their development in the central lymphoid organs, anergy induction in autoreactive lymphocytes before their emigration to the periphery, or production regulatory T lymphocytes that suppress the activation, proliferation, and differentiation of various effector cells. The major regulatory T lymphocytes display their phenotype as CD4(+)CD25(+)Foxp3(+) and constitute about 10% of the peripheral T lymphocytes. Even with these safeguards, the immunologic tolerance sometimes fails and generates autoimmune diseases. Scientists studying the pathogenesis of autoimmune diseases pay particular attention to a CD4(+) T lymphocytes subset, Th17 lymphocytes, distinct from Th1 and Th2. Th17 produces diverse proinflammatory cytokines including IL-17 and TNF-alpha. Th17 and these cytokines are causatively associated with many episodes of autoimmune diseases. Accumulated data reveal the critical role of Th17 cells in the pathology of autoimmunity and portray them as an important target in the treatment of various autoimmune diseases. In this article, we will describe the main characteristics of regulatory T cells and Th17 cells and their cellular and molecular mechanisms of protective or destructive functions, respectively.
Autoimmune Diseases ; Autoimmunity ; Cytokines ; Emigration and Immigration ; Immune System ; Interleukin-17 ; Lymphocytes ; Phenotype ; T-Lymphocytes ; T-Lymphocytes, Regulatory ; Th17 Cells ; Tumor Necrosis Factor-alpha

BACKGROUND: Prostaglandins (PGs) play pathogenic and protective roles in inflammatory diseases. The novel concept of PGs as immune modulators is being documented by several investigators. By establishing an in vitro experimental model containing human follicular dendritic cell-like cells, HK cells, we reported that HK cells produce prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2) and that these PGs regulate biological functions of T and B cells. METHODS: To investigate the respective contribution of cyclooxygenase-1 (COX-1) and COX-2 to PGE2 and PGI2 production in HK cells, we performed siRNA technology to knock down COX enzymes and examined the effect on PG production. RESULTS: Both PGE2 and PGI2 productions were almost completely inhibited by the depletion of COX-2. In contrast, COX-1 knockdown did not significantly affect PG production induced by lipopolysaccharide (LPS). CONCLUSION: The current results suggest that mPGES-1 and PGIS are coupled with COX-2 but not with COX-1 in human follicular dendritic cell (FDC) and may help understand the potential effects of selective COX inhibitors on the humoral immunity.
Cyclooxygenase 1 ; Cyclooxygenase 2 ; Dendritic Cells, Follicular ; Dinoprostone ; Epoprostenol ; Humans ; Immunity, Humoral ; Intramolecular Oxidoreductases ; Models, Theoretical ; Prostaglandins ; Research Personnel ; RNA, Small Interfering ; Stromal Cells

The mosquito-borne pathogen Zika virus may result in neurological disorders such as Guillain–Barré syndrome and microcephaly. The virus is classified as a member of the Flaviviridae family and its wide spread in multiple continents is a significant threat to public health. So has created a need to develop animal models to examine the pathogenesis of the disease and develop vaccines. To examine the clinical profile during Zika virus infection, we infected neonatal and adult wild-type mice (C57BL/6 and Balb/c) and compared the clinical signs of African-lineage strain (MR 766) and Asian-lineage strain (PRVABC59, MEX2-81) of Zika virus. Consistent with previous reports, eight-week-old female Balb/c mice infected with these viral strains showed no changes in body weight, survival rate, and no neurologic signs, but demonstrated increases in the weights of spleens and hearts. However, one-day-old neonates showed significantly lower survival rate and body weight with the African-lineage strain than the Asian-lineage strain. These results confirmed the pathogenic differences between Zika virus strains. We also evaluated the clinical responses in neonatal and adult mice of different strains. Our findings suggest that these are useful mouse models for characterization of Zika virus for vaccine development.

The mosquito-borne pathogen Zika virus may result in neurological disorders such as Guillain–Barré syndrome and microcephaly. The virus is classified as a member of the Flaviviridae family and its wide spread in multiple continents is a significant threat to public health. So has created a need to develop animal models to examine the pathogenesis of the disease and develop vaccines. To examine the clinical profile during Zika virus infection, we infected neonatal and adult wild-type mice (C57BL/6 and Balb/c) and compared the clinical signs of African-lineage strain (MR 766) and Asian-lineage strain (PRVABC59, MEX2-81) of Zika virus. Consistent with previous reports, eight-week-old female Balb/c mice infected with these viral strains showed no changes in body weight, survival rate, and no neurologic signs, but demonstrated increases in the weights of spleens and hearts. However, one-day-old neonates showed significantly lower survival rate and body weight with the African-lineage strain than the Asian-lineage strain. These results confirmed the pathogenic differences between Zika virus strains. We also evaluated the clinical responses in neonatal and adult mice of different strains. Our findings suggest that these are useful mouse models for characterization of Zika virus for vaccine development.

Porcine epidemic diarrhea (PED) is characterized by acute enteritis, watery diarrhea, weight loss, dehydration, and death with high mortality in neonatal piglets. In this study, 3 virus isolates collected in Vietnam between 2016 and 2017 were successfully propagated in Vero cells at high virus titers. Sequence analysis of the full-length spike (S) gene revealed that all 3 isolates belong to genogroup 2a, which is closely related to other prevalent Asian strains. Amino acid sequence comparisons revealed 98.19% to 99.13% homology with the Vietnam isolates circulating during 2013–2015, suggesting that field PED viruses (PEDVs) evolve continuously. Experiments in animals demonstrated that antisera from guinea pigs immunized with the vaccine strain resulted in higher levels (5 log2) of neutralizing antibody against the homologous strain, and showed a relatively lower level of neutralizing antibody against the field isolates. This finding would be helpful in choosing a PEDV strain for vaccine development.