The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease

Afzali, Behdad; Lombardi, Giovanna; Lechler, Robert I.; Lord, Graham M.

doi:10.1111/j.1365-2249.2007.03356.x

Cited by 655 publications

(504 citation statements)

References 231 publications

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“…32 Animal studies have suggested a mutually exclusive differentiation of CD4 þ cells into either Th17 or T reg , depending on the presence (Th17) or absence (T reg ) of IL-6. 33 The Th17 subset is important in the development of inflammation and autoimmunity, while T regs may downregulate inflammatory activity in autoimmune diseases and inhibit graft rejection in organ transplantation.…”

Section: Pathogenesismentioning

confidence: 99%

Bronchiolitis obliterans after allo-SCT: clinical criteria and treatment options

Uhlving

Buchvald

Heilmann

et al. 2011

Bone Marrow Transplant

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Bronchiolitis obliterans (BO) following allogeneic haematopoietic SCT (HSCT) is a serious complication affecting 1.7-26% of the patients, with a reported mortality rate of 21-100%. It is considered a manifestation of chronic graftversus-host disease, but our knowledge of aetiology and pathogenesis is still limited. Diagnostic criteria are being developed, and will allow more uniform and comparable research activities between centres. At present, no randomised controlled trials have been completed that could demonstrate an effective treatment. Steroids in combination with other immunosuppressive drugs still constitute the backbone of the treatment strategy, and results from our and other centres suggest that monthly infusions of high-dose pulse i.v. methylprednisolone (HDPM) might stabilise the disease and hinder progression. This article provides an overview of the current evidence regarding treatment options for BO and presents the treatment results with HDPM in a paediatric national HSCT-cohort.

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Section: Pathogenesismentioning

confidence: 99%

Bronchiolitis obliterans after allo-SCT: clinical criteria and treatment options

Uhlving

Buchvald

Heilmann

et al. 2011

Bone Marrow Transplant

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“…In contrast, CD4 + CD25 + FoxP3 + T regulatory cells (Tregs) actively restrain the inflammatory response, suppress development of autoimmune diseases and dampen a wide spectrum of immune responses (2,3). Furthermore, Th17 contributes to the transplant rejection while Tregs exhibit protective effects (4). Intriguingly, pathogenic Th17 and immunosuppressive Tregs from naïve CD4 cells are reciprocally induced, contingent upon the presence of either IL-6 or IL-2, respectively, in the presence of transforming growth factorbeta (TGFβ) (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Rapamycin inhibits differentiation of Th17 cells and promotes generation of FoxP3+ T regulatory cells

Kopf

Rosa

Howard

et al. 2007

International Immunopharmacology

236

183

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Reciprocal differentiation of immunosuppressive CD4 + CD25 + FoxP3 + T regulatory cells (Tregs) and proinflammatory IL-17-producing cells (Th17) from naïve CD4 cells is contingent upon the cytokine environment. Using MACS-purified CD4 cells, we found that rapamycin and cyclosporine A (CsA) potently inhibited the TGFβ and IL-6-induced generation of IL-17-producing cells. Intriguingly, rapamycin promoted, while CsA markedly inhibited, TGFβ-mediated generation of Tregs. The aforementioned effects of rapamycin and CsA were also observed for Flow-sorted CD4+CD25− T cells, indicating that the effect of these two immunosuppressive agents was based on their action on de novo generation of Tregs and Th17 cells from naïve CD4 cells. Our observation suggests a distinct mode of immunosuppressive action and tolerance induction by rapamycin and CsA. The capacity of rapamycin to generate immunosuppressive Tregs and to suppress differentiation of pathogenic Th17 cells furthers our understanding of the basis for the therapeutic immunosuppressive effects of rapamycin in patients with autoimmune diseases and allo-transplantation reactions.

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“…The reaction of such an immune response may benefit autoimmune diseases, but exacerbate chronic viral infections such as chronic HCV and HBV infections, because the balance of Th1/Th2 response is shifted toward Th1 in autoimmune reaction (Crane and Forrester, 2005;Afzali et al, 2007) and skewed toward Th2 in the immune response of chronic HBV and HCV infections (Bertoletti et al, 1997;Rossol et al, 1997;Tsai et al, 1997). The explanation for this scenario remains elusive.…”

Section: Discussionmentioning

confidence: 98%

Single-Nucleotide Polymorphism at CYP27B1-1260, but Not VDR Taq I, Is Possibly Associated with Persistent Hepatitis B Virus Infection

Zhu

Li²,

Han³

et al. 2012

Genetic Testing and Molecular Biomarkers

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Background: Vitamin D, beyond its role in calcium and bone metabolism, exhibits immunomodulatory effects on innate and adaptive immune pathways and is suggestively related to liver diseases. Objective: This study investigated the association of single-nucleotide polymorphisms in genes involved in vitamin D functions with hepatitis B virus (HBV) infection. Methods: Five hundred Chinese Han subjects, including 274 chronic HBV patients, 68 HBV infection resolvers, and 158 healthy controls without HBV infection, were studied. The CYP27B1-1260 promoter and the VDR Taq I polymorphisms were genotyped by polymerase chain reactionrestriction fragment length polymorphism. Results: Although there was no difference between HBV patients and healthy controls, HBV patients and healthy controls had a higher frequency of the CYP27B1-1260 genotype CC (15.0% vs. 2.9%, p = 0.004 and 13.3% vs. 2.9%, p = 0.006, respectively) and allele C (38.3% vs. 25.7%, p = 0.006 and 39.2% vs. 25.7%, p = 0.006, respectively) compared with resolvers. The genotype and allele frequencies of the VDR Taq I polymorphism had no difference between patients, resolvers, and healthy controls. Conclusion: These results suggest that the CYP27B1-1260 promoter polymorphism is possibly associated with the persistence, but not susceptibility to HBV infection in Chinese HBV patients, and that the VDR Taq I polymorphism is not suggested to be related to chronic HBV infection.

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The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease

Cited by 655 publications

References 231 publications

Bronchiolitis obliterans after allo-SCT: clinical criteria and treatment options

Bronchiolitis obliterans after allo-SCT: clinical criteria and treatment options

Rapamycin inhibits differentiation of Th17 cells and promotes generation of FoxP3+ T regulatory cells

Single-Nucleotide Polymorphism at CYP27B1-1260, but Not VDR Taq I, Is Possibly Associated with Persistent Hepatitis B Virus Infection

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