Dehydrodiconiferyl alcohol (DHCA) modulates the differentiation of Th17 and Th1 cells and suppresses experimental autoimmune encephalomyelitis.

Dehydrodiconiferyl alcohol (DHCA), originally isolated from the stems of Cucurbita moschata, has previously been shown to exhibit anti-adipogenic and anti-lipogenic effects in 3T3-L1 cells and primary mouse embryonic fibroblasts (MEFs) (Lee et al., 2012). Here, we investigated whether synthetic DHCA could suppress the CD4 T helper 17 (Th17)-mediated production of the interleukin (IL)-17 protein. The results from RT-qPCR suggest that DHCA-mediated down-regulation of IL-17 occurred at the transcriptional level by suppressing the expression of RAR-related orphan receptor (ROR)γt, the master transcription factor involved in the differentiation of Th17 cells. Furthermore, such inhibition was mediated by the suppression of NF-κB activity. DHCA also inhibited the Th1-mediated production of interferon (IFN) γ by controlling the expression of a key transcription factor known to regulate the production of this cytokine, T-bet. In the mouse experimental autoimmune encephalomyelitis (EAE) model, DHCA showed significant therapeutic effects by inhibiting the infiltration of immune cells into the spinal cords, decreasing the differentiation of pathogenic Th17 and Th1 cells, suppressing the expression of various pro-inflammatory cytokines, and eventually ameliorating the clinical symptoms of EAE mice. Taken together, our data indicate that DHCA may be a potential candidate as an agent for the control of Th17 and Th1-mediated inflammatory diseases.

Lee J ，Choi J ，Lee W ，Ko K ，Kim S ... -  《-》

A novel human truncated IL12rβ1-Fc fusion protein ameliorates experimental autoimmune encephalomyelitis via specific binding of p40 to inhibit Th1 and Th17 cell differentiation.

Guo W ，Wang C ，Wang X ，Luo C ，Yu D ，Wang Y ，Chen Y ，Lei W ，Gao X ，Yao W ... -  《Oncotarget》

Arctigenin Suppress Th17 Cells and Ameliorates Experimental Autoimmune Encephalomyelitis Through AMPK and PPAR-γ/ROR-γt Signaling.

Li W ，Zhang Z ，Zhang K ，Xue Z ，Li Y ，Zhang Z ，Zhang L ，Gu C ，Zhang Q ，Hao J ，Da Y ，Yao Z ，Kong Y ，Zhang R ... -  《-》

T-bet is essential for Th1-mediated, but not Th17-mediated, CNS autoimmune disease.

T cells that produce both IL-17 and IFN-γ, and co-express ROR-γt and T-bet, are often found at sites of autoimmune inflammation. However, it is unknown whether this co-expression of T-bet with ROR-γt is a prerequisite for immunopathology. We show here that T-bet is not required for the development of Th17-driven experimental autoimmune encephalomyelitis (EAE). The disease was not impaired in T-bet(-/-) mice and was associated with low IFN-γ production and elevated IL-17 production among central nervous system (CNS) infiltrating CD4(+) T cells. T-bet(-/-) Th17 cells generated in the presence of IL-6/TGF-β/IL-1 and IL-23 produced GM-CSF and high levels of IL-17 and induced disease upon transfer to naïve mice. Unlike their WT counterparts, these T-bet(-/-) Th17 cells did not exhibit an IL-17→IFN-γ switch upon reencounter with antigen in the CNS, indicating that this functional change is not critical to disease development. In contrast, T-bet was absolutely required for the pathogenicity of myelin-responsive Th1 cells. T-bet-deficient Th1 cells failed to accumulate in the CNS upon transfer, despite being able to produce GM-CSF. Therefore, T-bet is essential for establishing Th1-mediated inflammation but is not required to drive IL-23-induced GM-CSF production, or Th17-mediated autoimmune inflammation.

O'Connor RA ，Cambrook H ，Huettner K ，Anderton SM ... -  《-》

Simvastatin ameliorates experimental autoimmune encephalomyelitis by inhibiting Th1/Th17 response and cellular infiltration.

de Oliveira DM ，de Oliveira EM ，Ferrari Mde F ，Semedo P ，Hiyane MI ，Cenedeze MA ，Pacheco-Silva A ，Câmara NO ，Peron JP ... -  《-》