Curcumin Attenuates Acute Graft-versus-Host Disease Severity via In Vivo Regulations on Th1, Th17 and Regulatory T Cells

Abstract

BackgroundIn this study we examined the in vivo and in vitro effects and mechanisms of action of curcumin on the development of acute graft-versus-host disease (GVHD) using a murine model.Methodology/Principal FindingsMixed lymphocyte reactions were used to determine the in vitro effects of curcumin. Treatment with curcumin attenuated alloreactive T cell proliferation and inhibited the production of interferon (IFN)-γ and interleukin (IL)-17. In a murine acute GVHD model, transplantation of curcumin-treated allogeneic splenocytes into irradiated recipient mice significantly reduced the clinical severity scores of acute GVHD manifested in the liver, skin, colon and lung as compared with animals receiving vehicle-treated splenocytes. c-Fos and c-Jun expression levels in the skin and intestine, which are major target organs, were analyzed using immunohistochemical staining. Expression of both proteins was reduced in epithelial tissues of skin and intestine from curcumin-treated GVHD animals. The IFN-γ-expressing CD4+ splenocytes and IFN-γ-expressing lymph node cells were dramatically decreased in curcumin-treated mice. In contrast, CD4+Foxp3+ splenocytes were increased in the curcumin-treated acute GVHD animals. Flow cytometric analysis revealed that animals transplanted with curcumin-treated allogeneic splenocytes showed increased populations of CD4+ regulatory T cells (Tregs) as well as CD8+ Treg cells, compared to animals administered vehicle-treated splenocytes. Curcumin-treated acute GVHD animals could have a change in B cell subpopulations.Conclusion/SignificanceIn the present study, we investigated the efficacy and mechanism of action of curcumin treatment against acute GVHD. The acute GVHD mice administered with curcumin-treated splenocytes showed significantly reduced severity of acute GVHD. Curcumin exerted in vivo preventive effects on acute GVHD by reciprocal regulation of T helper 1 (Th1) and Treg (both CD4+ and CD8+ Treg) cell lineages as well as B cell homeostasis.

Oral Curcumin (Meriva) Is Effective as an Adjuvant Treatment and Is Able to Reduce IL-22 Serum Levels in Patients with Psoriasis Vulgaris

“…As previously reported, curcumin can be effective in treating psoriasis by affecting several pathogenetic pathways. Moreover, recent studies performed in autoimmune models suggest that curcumin can modulate T helper immune responses, downregulating the Th1 and Th17 cell pathways [ 39 , 40 ]. Accordingly, such activities might operate even in psoriasis.…”

Therapeutic effects of curcumin in inflammatory and immune‐mediated diseases: A nature‐made jack‐of‐all‐trades?

“…An important adverse effectc of allogenic hematopoietic stem cell transplantation (HSCT) is GVHD (Graft‐versus‐Host Disease), which can occur after bone marrow transplantation (BMT) (Park et al, ). Acute GVHD is an immune response driven mainly by Th1 and Th17 cells (Park et al, ). Curcumin is known to inhibit allo reactive T cell responses, IFN‐γ (secreted by Th1 cells), IL‐17 (secreted by Th17 cells), and AP‐1 activity production in vitro (Park et al, ).…”

“…Acute GVHD is an immune response driven mainly by Th1 and Th17 cells (Park et al, 2013). Curcumin is known to inhibit allo reactive T cell responses, IFN-γ (secreted by Th1 cells), IL-17 (secreted by Th17 cells), and AP-1 activity production in vitro (Park et al, 2013). inevitably hve the potential to induce adverse side effects, so it is strongly recommended that clinical applications be undertaken to use the immunomodulatory effects of curcumin in the treatment of patients with immune-mediated diseases.…”

White matter damage after traumatic brain injury: A role for damage associated molecular patterns

“…In addition, curcumin, a curry spice that we found to improve TBI outcomes [243], attenuated expression of RORγT, a transcription factor involved in T H 17 differentiation, decreased myelin basic protein-autoreactive T cells, and blocked the production of IL-17, the signature cytokine released by T H 17 cells, after EAE [277]. Curcumin also attenuated T H 17 production in ovalbumin-sensitized mice and in acute graft vs. host disease [278, 279]. As such, treatment strategies targeting T H 17 production and/or activity may provide a potential option to improve long-term outcomes.…”