Primary cilia are conserved organelles that integrate extracellular cues into intracellular signals and are critical for diverse processes, including cellular development and repair responses. Deficit Show more
Primary cilia are conserved organelles that integrate extracellular cues into intracellular signals and are critical for diverse processes, including cellular development and repair responses. Deficits in ciliary function cause multisystemic human diseases known as ciliopathies. In the eye, atrophy of the retinal pigment epithelium (RPE) is a common feature of many ciliopathies. However, the roles of RPE cilia in vivo remain poorly understood. In this study, we first found that mouse RPE cells only transiently form primary cilia. We then examined the RPE in the mouse model of Bardet-Biedl Syndrome 4 (BBS4), a ciliopathy associated with retinal degeneration in humans, and found that ciliation in BBS4 mutant RPE cells is disrupted early during development. Next, using a laser-induced injury model in vivo, we found that primary cilia in RPE reassemble in response to laser injury during RPE wound healing and then rapidly disassemble after the repair is completed. Finally, we demonstrated that RPE-specific depletion of primary cilia in a conditional mouse model of cilia loss promoted wound healing and enhanced cell proliferation. In summary, our data suggest that RPE cilia contribute to both retinal development and repair and provide insights into potential therapeutic targets for more common RPE degenerative diseases. Show less
BACKGROUND Psoriasis is an autoimmune and autoinflammatory disorder that has a significant impact on patient quality of life. The aim of the study was to assess the immune profiles of patients with ps Show more
BACKGROUND Psoriasis is an autoimmune and autoinflammatory disorder that has a significant impact on patient quality of life. The aim of the study was to assess the immune profiles of patients with psoriasis with multiple cytokine analysis. MATERIAL AND METHODS Fifty-two male psoriatic patients and 24 healthy male volunteers were recruited. Granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-gamma), interleukin (IL)-1 beta, IL-2, Il-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-13, IL-17A, IL-18, IL-21, IL-22, IL-23, IL-27, and tumor necrosis factor (TNF)-alpha were measured in patients' serum with a Th1/Th2/Th9/Th17/Th22/Treg Cytokine 18-Plex Human ProcartaPlex Panel, based on Luminex xMAP technology. RESULTS The median fluorescence intensities of serum GM-CSF, IL-2, IL-5, IL-10, IL-13, IL-17A, IL-21, and IL-22 were not intensive enough to calculate the cytokine concentration. We observed elevated levels of IL-6 (P=0.001) and IL-9 (P=0.003) in patients, compared with the control group. The levels of IL-1beta (P=0.008) and IL-27 (P=0.006) were decreased. In patients with psoriatic arthritis, we noticed a decreased level of IL-9 compared with that in patients without arthritis (P=0.034). The levels of IL-12 (P<0.05) and IL-18 (P<0.05) correlated positively with the Psoriasis Area and Severity Index. We found negative correlations of IL-9 (P<0.05), IL-12 (P<0.05), and IL-23 (P<0.05) with the age of psoriatic patients; IL-12 (P<0.05) and IL-23 (P<0.05) with psoriasis duration; and IL-6 (P<0.05) and IL-9 (P<0.05) with the Nail Psoriasis Severity Index. CONCLUSIONS Multiple cytokine analysis seems to be an important form of individual immune profile assessment before treatment selection. Show less