Dendritic cell activation by combined exposure to anti-CD40 plus interleukin (IL)-12 and IL-18 efficiently stimulates anti-tumor immunity

Despite as yet limited clinical effectiveness, dendritic cell (DC)-based immunotherapy remains a promising approach for the treatment of cancer, but requires further improvement in its immunostimulatory effectiveness. Potent anti-tumor immunity often depends on the induction of type 1 (T(H)1) immune responses. Therefore, we combined different DC maturation stimuli that are known to induce T(H)1 immunity [anti-CD40, interleukin (IL)-12, IL-18], with the aim to trigger a T(H)1 driven anti-tumor CTL response. When compared with untreated DC or DC treated with anti-CD40 alone, DC matured with anti-CD40 plus IL-12 and IL-18 expressed significantly more IFN-gamma and IL-12, induced enhanced CD8(+…

Friend retrovirus infection of myeloid dendritic cells impairs maturation, prolongs contact to naïve T cells, and favors expansion of regulatory T cells

AbstractRetroviruses have developed immunmodulatory mechanisms to avoid being attacked by the immune system. The mechanisms of this retrovirus-associated immune suppression are far from clarified. Dendritic cells (DCs) have been attributed a decisive role in these pathogenic processes. We have used the Friend retrovirus (FV) mouse model in order to acquire further knowledge about the role of infection of DCs in virus-induced immunosuppression. About 20% of the myeloid DCs that were generated from the bone marrow of FV-infected mice carried FV proteins. The infection was productive, and infected DCs transmitted the virus in cell culture and in vivo. FV infection of DCs led to a defect in DC …

Ultraviolet B light attenuates the systemic immune response in central nervous system autoimmunity

Objective: Environmental conditions (eg, latitude) play a critical role in the susceptibility and severity of many autoimmune disorders, including multiple sclerosis (MS). Here, we investigated the mechanisms underlying the beneficial effects of immune regulatory processes induced in the skin by moderate ultraviolet B (UVB) radiation on central nervous system (CNS) autoimmunity. Methods: Effects of UVB light were analyzed in a murine model of CNS autoimmunity (experimental autoimmune encephalomyelitis). Additionally, patients with relapsing–remitting MS were treated with narrowband UVB phototherapy. Immunomodulatory effects were examined in skin biopsies, serum samples, and immune cells of …

IL-10 Controls Ultraviolet-Induced Carcinogenesis in Mice

Abstract UV radiation-induced immunosuppression contributes significantly to the development of UV-induced skin cancer by inhibiting protective immune responses. IL-10 has been shown to be a key mediator of UV-induced immunosuppression. To investigate the role of IL-10 during photocarcinogenesis, groups of IL-10+/+, IL-10+/−, and IL-10−/− mice were chronically irradiated with UV. IL-10+/+ and IL-10+/− mice developed skin cancer to similar extents, whereas IL-10−/− mice were protected against the induction of skin malignancies by UV. Because UV is able to induce regulatory T cells, which play a role in the suppression of protective immunity, UV-induced regulatory T cell function was analyzed…

ADF Winter School-An exciting concept of the Arbeitsgemeinschaft Dermatologische Forschung to connect young scientists and clinician scientists in Dermatology at the top of Germany

Cutaneous RANK-RANKL Signaling Upregulates CD8-Mediated Antiviral Immunity during Herpes simplex Virus Infection by Preventing Virus-Induced Langerhans Cell Apoptosis

Herpes simplex virus-type 1 (HSV-1) causes the majority of cutaneous viral infections. Viral infections are controlled by the immune system, and CD8(+) cytotoxic T-lymphocytes (CTLs) have been shown to be crucial during the clearance of HSV-1 infections. Although epidermal Langerhans cells (LCs) are the first dendritic cells (DCs) to come into contact with the virus, it has been shown that the processing of viral antigens and the differentiation of antiviral CTLs are mediated by migratory CD103+ dermal DCs and CD8 alpha(+) lymph node resident DCs. In vivo regulatory T-cells (Tregs) are implicated in the regulation of antiviral immunity and we have shown that signaling via the receptor activ…

UVB light attenuates the systemic immune response in CNS autoimmunity

45th meeting of the Arbeitsgemeinschaft Dermatologische Forschung

Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity

AbstractBackgroundMultiple sclerosis (MS) disease risk is associated with reduced sun exposure. This study assessed the relationship between measures of sun-exposure (vitamin D (vitD), latitude) and MS disease severity, the mechanisms of action, and effect-modification by medication and sun-sensitivity associated MC1R variants.MethodsTwo multi-center cohort studies (nNationMS=946, nBIONAT=991). Outcomes were the multiple sclerosis severity score (MSSS) and the number of Gd-enhancing lesion (GELs). RNAseq of four immune cell populations before and after UV-phototherapy of five MS patients.ResultsHigh serum vitD was associated with reduced MSSS (PNationMS=0.021; PBIONAT=0.007) and reduced ris…

Tc9 cells, a new subset of CD8+T cells, support Th2-mediated airway inflammation

Similar to T-helper (Th) cells, CD8(+) T cells also differentiate into distinct subpopulations. However, the existence of IL-9-producing CD8(+) T (Tc9) cells has not been elucidated so far. We show that murine CD8(+) T cells activated in the presence of IL-4 plus TGF-β develop into transient IL-9 producers characterized by specific IFN-γ and IL-10 expression patterns as well as by low cytotoxic function along with diminished expression of the CTL-associated transcription factors T-bet and Eomesodermin. Similarly to the CD4(+) counterpart, Tc9 cells required for their differentiation STAT6 and IRF4. Tc9 cells deficient for these master regulators displayed increased levels of Foxp3 that in t…