Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD4+CD25+ regulatory T (Treg) cells control the immune response to a variety of antigens, including self-antigens, and several models support the idea of the peripheral expansion of CD4+CD25+ Treg cells. Although hormones such as estrogen and alpha-melanocyte-stimulating hormone have been recently reported to expand the CD4+CD25+ Foxp3-expressing Treg cell compartment, little is known about the endogenous factors and mechanisms controlling the peripheral expansion of CD4+CD25+ Treg cells. In this study, we report on the capacity of the vasoactive intestinal peptide (VIP), an immunosuppressive neuropeptide, to induce functional Treg cells in vivo. The administration of VIP together with specific antigen to T cell receptor (TCR)-transgenic (Tg) mice results in the expansion of the CD4+CD25+, Foxp-3/neuropilin 1-expressing T cells, which inhibit responder T cell proliferation through direct cellular contact. In addition to the increase in the number of CD4+CD25+ Treg cells, VIP induces more efficient suppressors on a per-cell basis. The VIP-generated CD4+CD25+ Treg cells transfer suppression, inhibit delayed-type hypersensitivity in TCR-Tg hosts, and prevent graft-versus-host disease in irradiated hosts reconstituted with allogeneic bone marrow.
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PMID:Vasoactive intestinal peptide generates CD4+CD25+ regulatory T cells in vivo. 1620 28

Induction of antigen-specific tolerance is critical for autoimmunity prevention and immune tolerance maintenance. In addition to their classical role as sentinels of the immune response, dendritic cells (DCs) play important roles in maintaining peripheral tolerance through the induction/activation of regulatory T (T(reg)) cells. The possibility of generating tolerogenic DCs opens new therapeutic perspectives in autoimmune/inflammatory diseases. Characterizing endogenous factors that contribute to the development of tolerogenic DCs is highly relevant. We here report that the immunosuppressive neuropeptide vasoactive intestinal peptide (VIP) induces the generation of human tolerogenic DCs with the capacity to generate CD4 and CD8 T(reg) cells from their respective naive subsets. The presence of VIP during the early stages of DC differentiation from blood monocytes generates a population of IL-10-producing DCs unable to fully mature after the effects of inflammatory stimuli. CD4 T(reg) cells generated with VIP-differentiated DCs resemble the previously described Tr1 cells in terms of phenotype and cytokine profile. CD8 T(reg) cells generated with tolerogenic VIP DCs have increased numbers of IL-10-producing CD8(+)CD28(-)-CTLA4(+) T cells. CD4 and CD8 T(reg) cells primarily suppress antigen-specific T(H)1-mediated responses. Therefore, the possibility of generating or expanding ex vivo tolerogenic DC(VIPs) opens new therapeutic perspectives for treating autoimmune diseases and graft-versus-host disease after allogeneic transplantation in humans.
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PMID:Vasoactive intestinal peptide generates human tolerogenic dendritic cells that induce CD4 and CD8 regulatory T cells. 1639 28

Acute graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in patients undergoing allogeneic bone marrow transplantation (BMT) for the treatment of leukemia and other immunogenetic disorders. The use of tolerogenic dendritic cells (DCs) that induce the generation/activation of regulatory T (Tr) cells for the treatment of acute GVHD following allogeneic BMT has been recently established. Therefore, the identification of factors that contribute to the development of tolerogenic DCs is highly relevant. We report on the use of the known immunosuppressive neuropeptide, the vasoactive intestinal peptide (VIP), as a new approach to induce tolerogenic DCs with the capacity to prevent acute GVHD. DCs differentiated in the presence of VIP impair allogeneic haplotype-specific responses of donor CD4(+) cells in mice given transplants by inducing the generation of Tr cells in the graft. VIP-induced tolerogenic DCs did not abrogate the graft-versus-leukemia response presumably by not affecting the cytotoxicity of transplanted T cells against the leukemic cells. Therefore, the inclusion of VIP-induced tolerogenic DCs in future therapeutic regimens may minimize the dependence on nonspecific immunosuppressive drugs used currently as antirejection therapy, and facilitate the successful transplantation from mismatched donors, by reducing the deleterious consequences of acute GVHD and extending the applicability of BMT.
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PMID:Vasoactive intestinal peptide induces regulatory dendritic cells that prevent acute graft-versus-host disease while maintaining the graft-versus-tumor response. 1641 27

CD4+ CD25+ regulatory T cells (Treg) control the immune response to a variety of antigens, including self-antigens, and several models support the idea of the peripheral generation of CD4+ CD25+ Treg from CD4+ CD25- T cells. However, little is known about the endogenous factors and mechanisms controlling the peripheral expansion of CD4+ CD25+ Treg. We have found that the immunosuppressive neuropeptide vasoactive intestinal peptide (VIP) induces functional Treg in vivo. The administration of VIP together with specific antigen to TCR-transgenic mice results in the expansion of the CD4+ CD25+, Foxp-3/neuropilin 1-expressing T cells, which inhibit responder T cell proliferation through direct cellular contact. The VIP-generated CD4+ CD25+ Treg transfer suppression, inhibiting delayed-type hypersensitivity in the hosts, prevent graft-versus-host disease in irradiated host reconstituted with allogeneic bone marrow, and significantly ameliorate the clinical score in the collagen-induced arthritis model for rheumatoid arthritis and in the experimental autoimmune encephalomyelitis model for multiple sclerosis.
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PMID:Vasoactive intestinal peptide generates CD4+CD25+ regulatory T cells in vivo: therapeutic applications in autoimmunity and transplantation. 1688 64

Induction of antigen-specific tolerance is critical to prevent autoimmunity, to maintain immune homeostasis, and to achieve transplant tolerance. In addition to their classic role as sentinels of the immune response, dendritic cells (DCs) play important roles in maintaining peripheral tolerance through the induction/activation of regulatory T (Treg) cells. The possibility of generating tolerogenic DCs opens new therapeutic perspectives in autoimmune and inflammatory diseases. Characterizing endogenous factors that contribute to the development of tolerogenic DCs is highly relevant. Some neuropeptides that are produced during the ongoing inflammatory response have emerged as endogenous anti-inflammatory agents that participate in the regulation of the processes that ensure self-tolerance. Here, we examine the latest research findings indicating that the role of these neuropeptides in immune tolerance is partially mediated through differential effects on DC functions, which depend on the differentiation and activation states. Importantly, neuropeptides such as vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide, and melanocyte-stimulating hormone have demonstrated an ability to induce tolerogenic DCs with the capacity to generate CD4 and CD8 Treg cells. The possibility of generating or expanding ex vivo tolerogenic DCs with neuropeptides indicates the therapeutic potential for autoimmune diseases and graft-versus-host disease after allogeneic transplantation in humans.
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PMID:Generating tolerogenic dendritic cells with neuropeptides. 1940 71

This paper reviews the research that has been conducted into the use of Sandostatin to control the debilitating symptoms of diarrhea in a number of different etiologies. These are cancer-related diarrheas, including diarrhea related to chemotherapy, radiotherapy, neuroendocrine tumor carcinoid syndrome, vasoactive intestinal peptide-secreting tumors and also non-cancer related diarrhea, including short bowel syndrome, ileo- and jejunostomy, dumping syndrome, graft versus host disease and AIDS-related diarrhea. There is an increasing recognition of the need to balance the cost of care with patient outcome. It is becoming clear that although the cost of a therapeutic regimen with Sandostatin is substantially greater than the current non-specific therapy, the overall cost is potentially greater without the use of Sandostatin for patients with refractory diarrhea due to the inevitable need for further treatment and/or hospitalization with intravenous fluid supplementation. Initial trials and reports from preclinical testing and clinical practice have shown promising results and, although in the majority of cases they strengthen the view taken in the published consensus guidelines for the use of Sandostatin for refractory diarrhea, further, larger scale, comparative clinical trials are required for any evidence-based definition of dosage and efficacy as a treatment or prophylactic agent to combat and control diarrhea.
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PMID:Diarrhea and the rationale to use Sandostatin. 2045 47