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Takashi Nishimura - One of the best experts on this subject based on the ideXlab platform.

  • immunosteroid as a regulator for Th1 Th2 Balance its possible role in autoimmune diseases
    Autoimmunity, 2005
    Co-Authors: Junko Matsuzaki, Takemasa Tsuji, Ikuo Imazeki, Hiroaki Ikeda, Takashi Nishimura
    Abstract:

    Immune Balance controlled by Th1 and Th2 cells is critical for the protection of host from pathogenic invasion while its imBalance becomes the cause of various immune disorders including autoimmune diseases. Cytokines, such as IL-12 and IL-4, are critical factor to drive the differentiation of naive CD4(+) T cells to Th1 or Th2 cells. In addition to cytokines, steroid hormones have been demonstrated to affect on the control of Th1/Th2 Balance and the onset of autoimmune diseases. Here, we will propose a new concept that immunosteroid, which is designated as a steroid produced by immunoregulatory cells, also play a critical role for regulation of Th1/Th2 Balance. First example of immunosteroid is Th2-dependently produced progesterone. Th2 cells, but not Th1 cells expressed P450scc and 20alpha-HSD and produced progesterone from 22R-hydroxycholesterol in cooperation with 3beta-HSD-expressing mouse fibroblasts. Th2-dependently produced progesterone induced apoptotic cell death of Th1 cells and inhibited the differentiation of Th1 cells. While Th2 cells were escaped from toxic effect of progesterone by metabolizing it to non-toxic 20alpha-hydroxyprogesterone with 20alpha-HSD. Second example of immunosteroid is dendritic cell (DC)-dependently produced 1alpha,25-dihydroxyvitamin D3 [1,25(OH)(2)D] secosteroid hormone, which has been demonstrated to inhibit autoimmune diseases. We found that 25-hydroxyvitamin D3 1alpha-hydroxylase, which metabolize 25-hydroxyvitamin D3 (inactive form) to 1,25(OH)(2)D was expressed in Th2-cytokine induced bone marrow-derived DC2 but not Th1-cytokine induced DC1. Moreover, 1,25(OH)(2)D was significantly inhibited DC1-induced type1 immunity. Thus, we initially demonstrated the critical role of immunosteroids in the control of Th1/Th2 Balance influencing on the onset of autoimmune diseases. Therefore, it will be an important issue to investigate the possible role of immunosteroids for the regulation of autoimmune diseases.

  • the restraint stress drives a shift in Th1 Th2 Balance toward Th2 dominant immunity in mice
    Immunology Letters, 1998
    Co-Authors: Kenji Iwakabe, Sonoko Habu, Masako Shimada, Akio Ohta, Takashi Yahata, Yasushi Ohmi, Takashi Nishimura
    Abstract:

    Abstract When mice were physically restrained in 50-ml tubes for 24 h, a marked decrease of NK activity was demonstrated in parallel with the elevation of serum corticosterone levels. The release of mice from restraint stress resulted in the recovery of NK activity, with a decrease of serum corticosterone levels within 48 h. Using this stress model, we also investigated the influence of restraint stress on mouse Th1/Th2 Balance. Consistent with the decrease of NK activity, IFN-γ production of mouse spleen cells greatly reduced after suffering from restraint stress. In contrast, the IL-4 producing ability of spleen cells was not so much affected by restraint stress. These results initially indicated that stress may induce the skewing of the Th1/Th2 Balance toward Th2-dominant immunity, which stimulates the occurrence of infectious diseases and allergic disorders.

Alexander Von Ruecker - One of the best experts on this subject based on the ideXlab platform.

  • shifts in the Th1 Th2 Balance during human pregnancy correlate with apoptotic changes
    Biochemical and Biophysical Research Communications, 1998
    Co-Authors: Gunter Reinhard, Arno Noll, H Schlebusch, P Mallmann, Alexander Von Ruecker
    Abstract:

    An important prerequisite for a successful pregnancy is that the maternal immune system does not reject the fetus. Down-regulation of the T helper 1 (Th1) associated cellular immune response could therefore be essential. With flow cytometric techniques, we show on a single cell level that both CD4+ and CD8+ T cells from peripheral blood produce less Th1 cytokines (i.e. IFN-gamma and IL-2) and more Th2 cytokines (i.e. IL-4) during normal human pregnancy and shortly after delivery than during non-pregnancy. The Th1/Th2 cytokine ratio in T cells of women during pregnancy and after delivery was significantly decreased. In contrast the Th1/Th2 ratio was elevated to near normal in women with recurrent spontaneous abortions, indicating a marked shift towards Th1 immunity. Fas antigen (CD95) on T cells was significantly elevated during pregnancy and in the post-delivery phase whereas the intracellular expression of anti-apoptotic protein Bcl-2 remained unchanged. Nevertheless Fas-mediated apoptosis in T cells was markedly reduced during normal human pregnancy. We hypothesize that Th1 cells undergo predominantly Fas-mediated apoptosis during pregnancy as has been shown in some Th2-prone diseases (e.g. SLE, HIV) where an elevated Fas expression on peripheral T cells is observed. This could explain the exacerbated occurrence of Th2-associated diseases in pregnancy.

  • surgical stress induces a shift in the type 1 type 2 t helper cell Balance suggesting down regulation of cell mediated and up regulation of antibody mediated immunity commensurate to the trauma
    Surgery, 1996
    Co-Authors: D Decker, Martin Schondorf, F Bidlingmaier, A Hirner, Alexander Von Ruecker
    Abstract:

    Background. Measuring serum cytokines, pituitary hormones, or acute phase proteins during or after surgery is not an optimal method for quantifying the impact of surgical procedures. In an effort to assess surgical stress by means of the immune response, we focused on changes in cell-mediated and antibody-mediated immunity as illustrated by the type 1/type 2 T-helper (Th1/Th2) cell Balance. The sensitivity of this approach was evaluated by comparing laparoscopic and conventional cholecystectomy (LCE, CCE). Methods. In a pragmatic prospective study 43 patients with symptomatic cholelithiasis were operated on either by LCE (n=25) or CCE (n=18). Blood sampling was done 24 hours before surgery, immediately before incision, and 2, 24, and 48 hours after surgery. Cell surface markers and cytokine production were used to characterize the Th1/Th2 Balance and were measured by means of flow cytometry and enzyme-linked immunosorbent assay techniques. Results. Activation of Th2 cells evokes the production and secretion of interleukin-4 (IL-4), which up-regulates the expression of immunoglobulin E receptors (FœRII, CD23) on B cells. Phytohemagglutinin-induced IL-4 production in freshly isolated peripheral blood mononuclear cells from patients increased more after CCE than LCE (IL-4, +41% versus +17%; p Conclusions. This study shows that surgical stress induces a shift in the Th1/Th2 Balance toward Th2, suggesting that cell-mediated immunity is down-regulated and antibody-mediated immunity is up-regulated after surgery. The evaluation of this shift may be clinically meaningful and help quantify even less invasive surgical procedures. When comparing CCE and LCE in this not strictly randomized study, we found LCE to be the less stressful procedure.

Xia Liu - One of the best experts on this subject based on the ideXlab platform.

  • microrna124 il6r mediates the effect of nicotine in inflammatory bowel disease by shifting Th1 Th2 Balance toward Th1
    Frontiers in Immunology, 2020
    Co-Authors: Zhen Qin, Pengyuan Wang, Jingjing Wan, Yu Zhang, Jie Wei, Yang Sun, Xia Liu
    Abstract:

    Epidemiological investigations have shown that smoking ameliorates ulcerative colitis (UC) but exacerbates Crohn's disease (CD), diseases that feature a Th2-mediated and Th1-mediated response, respectively. Cigarette extracts, especially nicotine, affect the Th1/Th2 Balance. We previously reported that nicotine protects against mouse DSS colitis (similar to UC) by enhancing microRNA-124 (miR-124) expression. Intriguingly, elevation of miR-124 in CD is reported to aggravate the disease. Here we investigate the dual regulation of miR-124 in inflammatory bowel diseases (IBDs), which may explain the similar bidirectional regulation of tobacco. We found that overexpressed miR-124 protected against mouse DSS-induced colitis with a Th1 polarization in peripheral blood lymphocytes and colon tissues, which was also found in human peripheral blood lymphocytes. Conversely, miR-124 knockdown worsened DSS murine colitis with a Th2 polarization. Moreover, knockdown of miR-124 could eliminate the polarization toward Th1 after nicotine treatment, suggesting that miR-124 mediates the effect of nicotine on the Th1/Th2 Balance. In addition, interference of IL-6R, which is a downstream target of miR-124, could remarkably weaken the Th1 polarization induced by miR-124. Taken together, these results suggest that nicotine shifts the Balance of Th1/Th2 toward Th1 via a miR-124-mediated IL-6R pathway, which might explain its dual role in IBDs.

  • microrna124 il6r mediates the effect of nicotine in inflammatory bowel disease by shifting Th1 Th2 Balance toward Th1
    Social Science Research Network, 2019
    Co-Authors: Zhen Qin, Pengyuan Wang, Jingjing Wan, Yu Zhang, Jie Wei, Yang Sun, Xia Liu
    Abstract:

    Background: Although it is generally believed that smoking protects against Th2-type ulcerative colitis (UC) and worsens Th1-type Crohn's disease (CD), the mechanism remains elusive. Nicotine is the main component of bidirectional regulation of tobacco on inflammatory bowel disease (IBD). Our previous studies have revealed that nicotine specifically elevates miR-124 level and protects against dextran sulfate sodium (DSS) colitis (resembling UC), while others reported that miR-124 is also highly expressed in CD, but it worsens CD. We speculated that miR-124 might mediate the dual role of nicotine in IBD by regulating Th1/Th2 Balance. Methods: Murine inflammation performance was evaluated by body weight change, disease activity index score (DAI), colon length, HE staining and score. Th1/Th2 Balance was detected by flow cytometry (FCM), cytometric bead array (CBA), ELISA and western blot in isolated peripheral blood lymphocytes and murine colon tissues. Findings: Results showed that miR-124 overexpression protected against DSS-induced colitis with a Th1 polarization in murine peripheral blood lymphocytes and colon tissues, while miR-124 knockdown showed opposite effect. Similar results were obtained in human peripheral blood lymphocytes. Furthermore, miR-124 knockdown could abolish Th1 polarization effect of nicotine on DSS mice and human peripheral blood lymphocytes. IL-6R interference could significantly attenuate the role of miR-124 in Th1 polarization, indicating it is a downstream target of miR-124 on Th1/Th2 Balance. Interpretation: Nicotine shifts Th1/Th2 Balance toward Th1 through miR-124-IL-6R pathway, which might be responsible for its dual role in IBD. Funding Statement: National Natural Science Foundation of China (81773726, 81603116) and Shanghai Sailing Program (19YF1459500). Declaration of Interests: The authors declare no financial or competing interests. Ethics Approval Statement: Human peripheral blood lymphocytes were collected from normal blood samples in Changhai Hospital, in accordance with the ethical standards of the institutional committee.

Kathryn J. Else - One of the best experts on this subject based on the ideXlab platform.

  • the essential role played by b cells in supporting protective immunity against trichuris muris infection is by controlling the Th1 Th2 Balance in the mesenteric lymph nodes and depends on host genetic background
    Frontiers in Immunology, 2019
    Co-Authors: Rinal Sahputra, Dominik Ruckerl, Kevin N Couper, Werner Muller, Kathryn J. Else
    Abstract:

    How B cells contribute to protective immunity against parasitic nematodes remains unclear, with their importance as accessory cells underexplored. In this study, anti-CD20 monoclonal antibody (α-CD20 mAb)-mediated depletion of B cells from C57BL/6 mice revealed an important role for B cells in supporting Th2 immune responses and thus expulsion of Trichuris muris (T. muris). C57BL/6 mice normally mount mixed Th1/Th2 immune responses to T. muris and expel the parasite by the third week post infection. However, B cell-depleted C57BL/6 had significantly reduced Th2-type cytokines post infection and failed to expel the parasite. IFN-γ production in the MLN of C57BL/6 mice receiving α-CD20 mAb treatment was not affected, collectively resulting in an overall change in Th1/Th2 Balance in favor of Th1. Further, the expression of IFN-γ and IFN-γ-induced genes at the effector site, the gut, was significantly increased in the absence of B cells. Interestingly, and in complete contrast, BALB/c mice, which mount strongly polarized Th2 immune responses, rather than mixed Th1/Th2 immune responses, were still able to expel T. muris in the absence of B cells. We thus hypothesized that the B cell plays a critical role in enabling strong Th2 responses in the context of mixed Th1/Th2 settings, with the role becoming redundant in highly Th2 polarized environments. In support of this, neutralization of IFN-γ in B cell depleted C57BL/6 restored resistance against T. muris infection. Thus, our data suggest an important role of B cells in supporting Th2-type immune responses in mixed IFN-γ-rich Th1/Th2 settings.

  • Increased susceptibility to oral Trichuris muris infection in the specific absence of CXCR5+ CD11c+ cells
    Parasite Immunology, 2018
    Co-Authors: Barry Bradford, Kathryn J. Else, Ruth Forman, David S. Donaldson, Neil A. Mabbott
    Abstract:

    : Trichuris muris is a natural mouse helminth pathogen which establishes infection specifically in the caecum and proximal colon. The rapid expulsion of T. muris in resistant mouse strains is associated with the induction of a protective T helper cell type 2 (Th2)-polarized immune response. Susceptible mouse strains, in contrast, mount an inappropriate Th1 response to T. muris infection. Expression of the chemokine CXCL13 by stromal follicular dendritic cells attracts CXCR5-expressing cells towards the B-cell follicles. Previous studies using a complex in vivo depletion model have suggested that CXCR5-expressing conventional dendritic cells (cDC) help regulate the induction of Th2-polarized responses. Here, transgenic mice with CXCR5 deficiency specifically restricted to CD11c+ cells were used to determine whether the specific absence CXCR5 on CD11c+ cells such as cDC would influence susceptibility to oral T. muris infection by affecting the Th1/Th2 Balance. We show that in contrast to control mice, those which lacked CXCR5 expression on CD11c+ cells failed to clear T. muris infection and developed cytokine and antibody responses that suggested a disturbed Th1/Th2 Balance with enhanced IFN-γ expression. These data suggest an important role of CXCR5-expressing CD11c+ cells such as cDC in immunity to oral T. muris infection.

Chiharu Kubo - One of the best experts on this subject based on the ideXlab platform.

  • an oral introduction of intestinal bacteria prevents the development of a long term Th2 skewed immunological memory induced by neonatal antibiotic treatment in mice
    Clinical & Experimental Allergy, 2002
    Co-Authors: Nobuyuki Sudo, Xiaonian Yu, Yuji Aiba, Naomi Oyama, Junko Sonoda, Yasuhiro Koga, Chiharu Kubo
    Abstract:

    Summary Background Recent epidemiological studies indicate that antibiotic use in infancy may be associated with an increased risk of developing atopy. Our previous work on animals demonstrated that kanamycin use during infancy promotes a shift in the Th1/Th2 Balance towards a Th2-dominant immunity. Objective The first purpose of this study is to clarify whether or not the supplementation of intestinal bacteria can reverse such a Th2-skewed response induced by neonatal antibiotic use. The second objective is to elucidate the contribution of genetic factors to antibiotic-induced immune-deviation. Methods BALB/c or C57BL/6 mice at 3 weeks of age were orally administered 600 µg/day of kanamycin sulphate for seven consecutive days. Thereafter, the mice were inoculated with one type of intestinal bacterial species: Enterococcus faecalis, Lactobacillus acidophilus or Bacteroides vulgatus. Blood samples were collected 10 weeks after the cessation of kanamycin treatment, and the effect of the kanamycin treatment on Th1/Th2 Balance was evaluated based on in vivo antibody levels. Results A kanamycin-induced elevation of the serum IgE levels was reversed by the supplementation with Enterococcus faecalis, and to a lesser extent by that with Lactobacillus acidophilus. The IgE/IgG2a ratio in the mice supplemented with Enterococcus faecalis significantly decreased in comparison with that in the kanamycin-treated mice without any bacterial supplementation, while such a ratio was enhanced in the mice inoculated with Bacteroides vulgatus. No antibiotic-induced Th2-skewed response was seen in C57BL/6 mice that are genetically biased towards Th1-dominant immunity. Conclusion These results suggest that adequate probiotic intervention after antibiotic treatment may improve the intestinal ecosystem, and thereby prevent the Th2-shifted immunity induced by neonatal antibiotic use. In addition, the difference of genetic backgrounds also contributes to such an antibiotic-induced Th2-skewed response.

  • antibiotic use during infancy promotes a shift in the Th1 Th2 Balance toward Th2 dominant immunity in mice
    The Journal of Allergy and Clinical Immunology, 2001
    Co-Authors: Naomi Oyama, Nobuyuki Sudo, Hiroshi Sogawa, Chiharu Kubo
    Abstract:

    Abstract Background: Recent epidemiologic studies indicate that antibiotic use in infancy may be associated with an increased risk of development of atopy; however, its precise mechanism remains to be elucidated. Objective: The purpose of this study is to clarify whether one such antibiotic, kanamycin, affects the T H 1/T H 2 Balance. Methods: BALB/c mice at 3 and 52 weeks of age were orally administered 600 mg/d kanamycin sulfate for 7 consecutive days. Blood samples were collected on weeks 0, 10, 18, and 26 after the cessation of kanamycin treatment, and the effect of the kanamycin treatment on the T H 1/T H 2 Balance was evaluated on the basis of both the in vivo antibody levels and the in vitro splenocyte cytokine secretion pattern. Results: The administration of kanamycin increased the serum levels of total IgG1 and IgE while decreasing the serum IgG2a levels. Moreover, when spleen cells were stimulated with immobilized anti-CD3 antibody in vitro, such kanamycin treatment enhanced the in vitro IL-4 secretion while reducing the in vitro IFN-γ secretion. The basal IL-12 p70 secretion levels of splenic dendritic cells in the kanamycin-treated mice were lower than those in the control mice, although no significant difference was seen in IL-12 p40 levels between either group of mice. Conclusion: These results suggested that antibiotic use during infancy may indeed quantitatively disturb, qualitatively disturb, or both the intestinal microflora and thereby prevent postnatal T H 1 cell maturation, thus resulting in a T H 2-polarized immune deviation. (J Allergy Clin Immunol 2001;107:153-9.)