The Mechanisms Of Abnormality Of Langerhans Cells From Patients With Psoriasis

Psoriasis is a disease characterized by inflammation and increased population of hyperproliferative keratinocytes. To date, its pathogenesis is still unknown. As a rule, immunity, heredity and infection have been implicated in the pathogenesis of this disease. Along with researching deep into dendritic cells (DCs) in immune fields, LCs which are paradigmatic DCs also become hotspots. A number of reports have suggested that LCs play a critical role in the pathogenesis of psoriasis. Therefore most researches about pathogenesis of psoriasis have focused on LCs. It has been proved that LCs isolated from psoriasis are abnormal. These abnormal LCs can activate T cells within epidermis. Morhenn et al proposed that cytokines from activated T cells could stimulate keratinocytes hyperproliferation. At the same time, hyperproliferative keratinocytes might express some cytokines that could migrate leukocytes into lesions. These are important features of psonasis. Therefore some investigators suggested that abnormal LCs might play a pivotal role in initiating psoriasis. So we assume that it is necessary to study the reason of LCs abnormalities for probing into the pathogenesis of psoriasis. Till now, it has been confirmed that the peripheral blood monocytes can differentiate into LCs in the presence of GM-C SF, IL-4 and TGF-13 1 in vitro. The human monocyte-derived LCs are immature DCs. After addition of LPS or 'TNF-cL, the cells become mature. With the development of culture techniques allowing the in vitro generation of LCs from human monocy'tes, ibecomes possible to stLldy the reason of LCs abnormality in psoriasis. Thialso benefits us to investigate from which stage LCs abnormality ariseseither from precursors or from LCs differentiation and maturation under thabnormal microenvironment suPplied by psoriatic lesional keratinocytes.Part l. The characterishcs of Langerhans cells (LC) derived from thImonocyt6s frOm the patientS with psoriasisTo investigate whether the abnormality of LCs in patients with psoriasiIarises from precursors, we analyse the characteristics of LCs derived froffthe monocytes of the patients cultured with the GM-CSF+IL-4+TGF-0l for 5days.At first, we observed the morphological characteristics of the LC5derived from the monocytes of the patients. The results showed that thirregUlar morphological cells wer present after culture 3 days later Only Efew cells grew adherently. After 5 days, pats of cells looked lilie branches.No significan difference was observed betWeen the morphology of LC5derived from the monocytes of the patients and the LCs from healthy blooddonors.Then we detected the phenotyPes of the LCs derived from themonocytes of the patients. The results showed that the exPressions of CD1aand CD86 on LCs derived from the monocytes of the patiellts were moderate.But the cells did not express CD83 and CD14. The phenoooes of LCsderived from the monocytes of the patients were same as the LCs fromhealthy blood donors.IL-l2 derived from LCs plays an important role in the initiation and thepersistence of T cell activation in the process of the antigen presentation. Sowe also examined the IL-l2 production of LCs derived from the monocytesof the patients by ELISA. The results demonstrated that IL-l2 level fromLCs derived from the monocytes of the patients was l0.6t3.1 pgiml. Incontrast, the IL-l2 levels from LCs derived from the monocytes of healthyblood donors was l3 .6f4.7pg/ml.We also tested the caPacity of LCs derived from the monocytes of thepatients to stimulate allogeneic T lymphocytes in MLR.The results showedthat the LCs derived from the monocytes of the patiellts could stimulateproliferation of allogeneic T cells. At the same time, the caPacity of LCsderived from the monocytes of healthy blood donors to achvae T cells is thesame as tha...