The interaction between the helicase DHX33 and IPS-1 as a novel pathway to sense double-stranded RNA and RNA viruses in myeloid dendritic cells

In eukaryotes, there are at least 60 members of the DExD/H helicase family, many of which are able to sense viral nucleic acids. By screening all known family members, we identified the helicase DHX33 as a novel double-stranded RNA （dsRNA） sensor in myeloid dendritic cells （mDCs）. The knockdown of DHX33 using small heteroduplex RNA （shRNA） blocked the ability of mDCs to produce type I interferon （IFN） in response to poly hC and reovirus. The HELICc domain of DHX33 was shown to bind poly hC. The interaction between DHX33 and IPS-1 is mediated by the HELICc region of DHX33 and the C-terminal domain of IPS-1 （also referred to MAVS and VISA）. The inhibition of DHX33 expression by RNA interference blocked the poly hC-induced activation of MAP kinases, NF-KB and IRF3. The interaction between the helicase DHX33 and IPS-1 was independent of RIG-I/MDA5 and may be a novel pathway for sensing poly I-C and RNA viruses in mDCs.

Improved survival ratios correlate with myeloid dendritic cell restoration in acute-on-chronic liver failure patients receiving methylprednisolone therapy

Acute-on-chronic liver failure （ACLF） is a severe life-threatening complication. Liver transplantation is the only available therapeutic option; however, several limitations have restricted its use in patients. The use of corticosteroids as an optional therapy for ACLF has received a great deal of interest. The rationale behind its use is the possible role of the immune system in initiating and perpetuating hepatic damage. In order to assess the relationship between myeloid dendritic cells （mDCs） and the efficacy of methylprednisolone （MP） treatment for hepatitis B virus （H BV）-associated ACLF patients, we recruited 30 HBV-associated ACLF patients who had received MP treatment at lO-day intervals; 26 patients received conservative medical （CM） management as a control. The functionality of DC subsets was lower in these ACLF patients compared with healthy subjects. In addition, compared with survivors, dead/transplanted patients had lower functional mDC in both groups. Furthermore, a decreased numbers of mDC at baseline was associated with high mortality of ACLF patients. Importantly, MP treatment resulted in a significant decrease in 28-day mortality, and all MP patients exhibited an initial rapid decrease in circulating mDC numbers within 10 days of MP treatment. Subsequently, MP survivors displayed a continuous increase in mDC numbers accompanied by a decrease in total bilirubin levels by more than 30%. However, MP dead/ transplanted patients lacked these sequential responses compared with survivors. This evidence suggests strongly that the higher mDC numbers at baseline and the recovery of mDC number at the end of treatment may represent a prognostic marker for favorable response to corticosteroid treatment in ACLF patients.

Changes in dendritic cells and dendritic cell subpopulations in peripheral blood of recipients during acute rejection after kidney transplantation

Background Advances in transplantation immunology show that the balance between dendritic cells （DCs） and their subsets can maintain stable immune status in the induction of tolerance after transplantation. The aim of this study was to investigate if DCs and DC subpopulations in recipient peripheral blood are effective diagnostic indicators of acute rejection following kidney transplantation. Methods Immunofluorescent flow cytometry was used to classify white blood cells （WBCs）, the levels of mononuclear cells and DCs （including the dominant subpopulations, plasmacytoid DC （pDC） and myeloid DC （mDC）） in peripheral blood at 0, 1, 7, and 28 days and 1 year after kidney transplantation in 33 patients. In addition, the blood levels of interleukin-10 （IL-10） and IL-12 were monitored before and after surgery. Fifteen healthy volunteers served as normal controls. Patients were undertaking hemodialysis owing to uremia before surgery. Results The total number of DCs, pDC, and mDC in peripheral blood and the pDC/mDC ratio were significantly lower in patients than controls （P 〈0.05）. Peripheral DCs suddenly decreased at the end of day 1, then gradually increased through day 28 but remained below normal levels. After 1 year, levels were higher than before surgery but lower than normal. The mDC levels were higher in patients with acute rejection before and 1 day after surgery （P 〈0.005）. There was no significant difference in IL-10 and IL-12 levels between patients with and without acute rejection. Conclusion The changes in DCs and DC subpopulations during the acute rejection period may serve as effective markers and referral indices for monitoring the immune state, and predicting rejection and reasonably adjusting immunosuppressants.