Thomas Schwarz

..The further characterisation of these cells will determine whether they can be applied in the future therapeutically with the ultimate aim to induce specific immunosuppression...

..The mechanisms involved and the biological as well as the potential therapeutic implications of these findings are discussed.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 63-66; doi:10.1038/jidsymp.2009.3...

..Studies addressing the molecular mechanisms underlying UV-induced immunosuppression will contribute to a better understanding how UV acts as a pathogen but on the other hand can be also used as a therapeutic tool...

..Perioral dermatitis (POD) is a common dermatosis without standard therapy...

..Further characterization of these cells will determine whether they can be applied therapeutically in the future with the ultimate aim to induce specific immunosuppression...

..In addition, these insights will contribute to a better understanding of photocarcinogenesis since suppression of the immune system by UVR essentially contributes to the induction of skin cancer...

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..Thus, suppression of the adaptive and induction of the innate immune system by UVR may be components of a physiological protection process. These insights might have effect on the future recommendations for daily sun protection...

..However, constant boosting of Treg with Ag doses in the challenging range results in final sensitization that might limit their therapeutic potential...

..Together, this may help explain the clinical benefits of ECP in prophylactic, acute, and therapeutic settings...

..Furthermore, CD86-mediated costimulation appears to play a more critical role in the protection against photocarcinogenesis than CD80...

..IL-23 shares with IL-12 the still unique capacity to restore suppressed immune responses because of its effect on Treg...

..It is essential that drugs applied to patients with AD restore the impaired epidermal barrier to prevent sensitization by environmental allergens...

..Though being primarily a proinflammatory cytokine through this capacity, IL-18 can also foster an immune response that is suppressed by UV radiation...

..These data identify a new mechanism by which IL-12 can restore immune responses and also demonstrate a link between DNA repair and the prevention of UV-induced immunosuppression by IL-12...

..Together, this indicates that activated UVR-Treg can alter APCs in such a way that they lose their sensitizing capacity but in turn induce Treg. Thus, UVR-Tregs switch APCs from a stimulatory to a regulatory phenotype...

..Transfer activity was lost when cells were depleted of CD4(+) or CD25(+) subpopulations. These data suggest that photopheresis exerts its immunomodulatory effects via the induction of Ag-specific regulatory T cells...

..Thus, a disturbed skin barrier may trigger AMP induction in AD and psoriasis. The functional role of AMP in AD, especially with regard to the control of S. aureus colonization, needs further analysis...

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..coli. This indicates that the antimicrobial response in AD is not generally impaired, but greatly differs according to the type of AMP produced by the skin...

..Our results indicate that TSP-1 downregulates cutaneous delayed-type hypersensitivity reactions by acting on several distinct pathways mediating skin inflammation...

..Therefore, environmental stimuli at the skin can rewire the local and systemic immune system by means of RANKL...

..This supports the concept that LCs are more important for the downregulation than the induction of immune responses in the skin...

..Together, these data indicate that IL-12 deficiency is associated with an increased risk to develop UV-induced skin cancer, implying that endogenous IL-12 may protect from photocarcinogenesis...

..v. injection. This finding shows that the migratory behavior can be reprogrammed by tissue-specific DC and may have input on strategies trying to use Treg not only for the prevention but also for the treatment of immune-mediated diseases...

..Although IR may delay the onset of UVR-induced tumors, it might contribute to a worse outcome by shifting these tumors into a more aggressive phenotype...

..This result may explain the clinical observation that prolonged treatment with topical corticosteroids sometimes leads to bacterial infection...

..On this in vitro treatment, Treg cells migrate into the skin and thus inhibit the elicitation of CHS...

..As, however, IR reduces UV-induced DNA damage, the balance between these two effects may be important. Thus, in vivo carcinogenesis studies are required to define the role of IR and its interaction with UV in photocarcinogenesis...

..The atypical clinical and histopathologic appearance of the melanocytic lesions as well as the course of disease may have been influenced by the immunosuppression...

..Together, our results show that overexpression of IL-15 in the epidermis enhances both innate and adaptive cutaneous immunity...

..For defense against bacteria, the innate immune response including the release of antimicrobial peptides is much more relevant than the adaptive immune response. Keratinocytes have the capacity to release antimicrobial peptides...

..Hence the previously reported UV-protective effects of GTP appear to be mediated in human cells via IL-12, most likely through induction of DNA repair...

..Our results show that cytokines can protect cells from apoptosis induced by DNA-damaging UV radiation by inducing DNA repair, and that nucleotide-excision repair can be manipulated by cytokines...

..Another major mechanism is the induction of immunosuppression. This review primarily focuses on recent advances in photoimmunology which will contribute to the further understanding how phototherapy acts...

..Detailed knowledge about the phenotype and mode of action of these cells will significantly increase our understanding of the pathogenesis of autoimmune diseases and will also help to identify new therapeutic strategies...

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..Owing to the lack of clinical trials, we recommend that patients be treated according to the existing guidelines for melanoma...

..v. injection, because they obviously do not migrate into the skin...

..ECM can be easily differentiated from the latter by its typical clinical features...

..Because pimecrolimus improved the epidermal barrier and did not cause atrophy, it might be more suitable for long-term treatment of AD...

..Hence, it is tempting to speculate that the activity of IL-12 to reduce UV-induced immunosuppression may be due at least partially to this new biological activity of IL-12...

..The following review will briefly discuss current aspects of the mechanisms involved in UV-induced signal transduction...

..This may have impact on the development of future strategies utilizing antibodies against IL-12 and IL-23, respectively, for the treatment of inflammatory dermatoses...

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..The clinical diagnosis of amelanotic melanoma is still a challenge...

..The following review will briefly discuss current aspects of the interplay between the different signaling pathways involved in UV-induced apoptosis...

..This study indicates that (i) the expression level and the processing status of FLIP may play a crucial role in determining the sensitivity of melanoma cells towards TRAIL and (ii) expression of FLIP is regulated by UVB...

..The following review will briefly discuss current aspects of the interplay between the different signaling pathways involved in UVB-induced apoptosis...

..This indicates that DNA damage, death receptor activation and ROS formation contribute to UVB-induced apoptosis in an essential and independent way...

..No dermatological diseases, trauma to the affected extremity or the spine, or familial pruritus were reported...

..Most of the effects of both ambient and therapeutic ultraviolet radiation are immunosuppressive in nature...

..Multiple erythema migrans represent an early stage of systemic infection. Thus early diagnosis and rapid initiation of therapy are warranted...

..Thus, a dysfunction of T cells, in addition to granulocytes, may contribute to the pathophysiology of leukocyte adhesion deficiency type I, which arises from mutations in the human CD18 gene...

..Mycophenolate mofetil was well tolerated and induced complete remission in 2 patients, and substantial improvement in the third patient...

..Basal cell carcinoma (BCC) in the nipple area is extremely rare and can be mistaken for Paget's disease...

..Melanoma of the penis is very rare, and the prognosis is poor. This could be the first case of a "kissing melanoma" of the penis reported in published studies...

..In contrast, injection of the interleukin-1-receptor antagonist anakinra caused a complete remission within a few days...

..These results reveal a previously unrecognized anti-inflammatory property of the angiogenesis inhibitor vasostatin, and suggest that vasostatin is a potential candidate drug for the treatment of inflammation...

..Moreover, these results point out the crucial role of Th1 responses and UV-induced regulatory T cell function in the protection against UV-induced tumor development...

..Artificial UV irradiation (UVA, PUVA) can also induce pigmentary disorders, including lentigines. Since the therapeutic options for UV-induced pigmentary changes are limited consequent protection as a prophylactic measure is recommended...

..Down-regulation of TRAIL might represent another example of a natural protection mechanism that is eliminated by chronic UV exposure...

..Moreover, sDec2-reactive T cells appear to represent the regulatory T cells responsible for mediating UV-induced tolerance...

..Thus, similar to nucleotide excision repair, taurine uptake is critically involved in photoprotection of the skin...

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..The treatment was well tolerated with no dose-related toxicity other than the targeted depletion of peripheral T cells. A pivotal study has been initiated based on these findings...

..Melanocortins such as alpha-MSH may therefore represent a novel class of modulators with potential usefulness for the treatment of fibrotic disorders...