The clinical extent of psoriasis pathology is regulated in part by defects in immune networks, including a defect in the suppressive actions of regulatory T cells. Recently, CD14(+) HLA-DR(-/low) monocytic myeloid-derived suppressor cells (Mo-MDSCs) have been shown to suppress T-cell activation as one of their suppressive mechanisms. However, little is known about the role of Mo-MDSCs and their functional relationship to T-cell suppression in relation to human chronic immune-mediated inflammatory diseases, including psoriasis. Despite psoriasis being a hyperinflammatory condition, Mo-MDSCs were elevated in psoriatic patient peripheral blood mononuclear cells compared to nonpsoriatic healthy controls (2.6% vs. 0.9%, P < 0.002). Freshly isolated psoriatic Mo-MDSCs directly suppressed CD8 T-cell proliferation less efficiently than healthy control Mo-MDSCs. In addition, psoriatic Mo-MDSCs expressed reduced surface expression of programmed cell death protein 1 compared to healthy controls. Additional in vitro assays also demonstrated that psoriatic and control Mo-MDSCs both induce regulatory T-cell conversion from naïve T effector cells, but, importantly, the regulatory T cells induced by psoriatic Mo-MDSCs displayed decreased suppressive functionality. These results suggest that aberrations in psoriatic Mo-MDSCs prevent proper suppression of effector T-cell expansion and hamper the immune system's ability to correctly self-regulate.

Background Liver parenchymal cell allografts initiate both CD4-dependent and CD4-independent, CD8+ T cell-mediated acute rejection pathways. The magnitude of allospecific CD8+ T cell in vivo cytotoxic effector function is maximal when primed in the presence of CD4+ T cells. The current studies were conducted to determine if and how CD4+ T cells might influence cytotoxic effector mechanisms. Methods Mice were transplanted with allogeneic hepatocytes. In vivo cytotoxicity assays and various gene-deficient recipient mice and target cells were utilized to determine the development of Fas-, TNF-α-, and perforin-dependent cytotoxic effectors mechanisms following transplantation. Results CD8+ T cells maturing in CD4-sufficient hepatocyte recipients develop multiple (Fas-, TNF-α-, and perforin-mediated) cytotoxic mechanisms. However, CD8+ T cells, maturing in the absence of CD4+ T cells, mediate cytotoxicity and transplant rejection that is exclusively TNF-α/TNFR-dependent. To determine the kinetics of CD4-mediated help, CD4+ T cells were adoptively transferred into CD4-deficient mice at various times posttransplant. The maximal influence of CD4+ T cells on the magnitude of CD8-mediated in vivo allocytotoxicity occurs within 48 hours. Conclusion The implication of these studies is that interference of CD4+ T cell function by disease or immunotherapy will have downstream consequences on both the magnitude of allocytotoxicity as well as the cytotoxic effector mechanisms employed by allospecific CD8+ cytolytic T cells.

Bilateral and unilateral UM patients share similar demographics, clinicopathological characteristics, treatments and prognoses. Moreover, the development of bilateral disease does not portend a poorer prognosis and patients should be treated similarly to those with unilateral disease.

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Cosmetic and laser procedures are increasingly popular among patients and are skills in which dermatologists are regarded as well trained. Most dermatology residents intend to incorporate cosmetic procedures into their practice and prefer to learn such procedures during residency through direct patient care. However, there are notable challenges in optimizing how residents are trained in cosmetic and laser dermatology. To address these barriers and elevate the practice of cosmetic dermatology in academic medicine, the Association of Academic Cosmetic Dermatology (AACD) was founded in 2021 as the lead professional society for dermatologists who direct the education of resident trainees in cosmetic and laser dermatology. The AACD, a group of board-certified dermatologists who teach cosmetic and laser dermatology to residents, aims to improve cosmetic dermatology education through collaboration, research, and advocacy.

BACKGROUND Most eyelid defects after Mohs micrographic surgery are referred to oculoplastic surgery or plastic surgery for reconstruction, but growing evidence suggests the safety of such repairs performed by dermatologic surgeons is equivalent if not better. Lateral canthotomy with inferior cantholysis may be used by the dermatologic surgeon to reconstruct larger lower eyelid defects. OBJECTIVE To demonstrate lateral canthotomy with inferior cantholysis performed by the dermatologic surgeon can result in safe, functionally and cosmetically acceptable surgical outcomes. MATERIALS AND METHODS An institutional review board-approved retrospective study of repairs performed by a single dermatologic surgeon between January 2013 and August 2019. Patient demographics, operative and follow-up notes were reviewed. Two cosmetic dermatologists assessed aesthetic results based on final follow-up photographs using a visual analogue scale. RESULTS Eight cases were included in the analysis. Seventy-five percent of patients were men, with a mean age of 74.1 years old. All tumors were basal cell carcinoma; the mean defect size was 2.4 cm2. No serious complications or postoperative interventions occurred. The median cosmetic score was 85.6 ± 11.5. CONCLUSION Dermatologic surgeons can safely perform repairs of lower eyelid defects with lateral canthotomy with inferior cantholysis, achieving satisfactory functional and cosmetic outcomes.

Allospecific T memory cell responses in transplant recipients arise from environmental exposure to previous transplantation or cross-reactive heterologous immunity. Unfortunately, these memory responses pose a significant barrier to the survival of transplanted tissue. We have previously reported that concurrent inhibition of CD154 and LFA-1 suppresses primary CD8-dependent rejection responses that are not controlled by conventional immunosuppressive strategies. We hypothesized that CD154- and LFA-1-mediated inhibition, by targeting activation as well as effector functions, may also be efficacious for the control of alloreactive CD8+ T cell responses in sensitized hosts. We found that treatment with anti-LFA-1 mAb alone enhanced transplant survival and reduced CD8-mediated cytotoxicity in sensitized CD4 KO recipients. However, treatment with anti-CD154 mAb alone did not have an effect. Notably, when both CD4- and CD8-dependent rejection pathways are operative (wild-type sensitized recipients), LFA-1 significantly inhibited CD8-mediated in vivo allocytotoxicity but did not correspond with enhanced hepatocyte survival. We hypothesized that this was due to alloantibody-mediated rejection. When anti-LFA-1 mAb treatment was combined with macrophage-depletion, which we have previously reported impairs alloantibody-mediated parenchymal cell damage, in vivo cytotoxic effector function was significantly decreased and was accompanied by significant enhancement of hepatocyte survival in sensitized wild-type recipients. Therefore, LFA-1 is a potent therapeutic target for reduction of CD8-mediated cytotoxicity in sensitized transplant recipients and can be combined with other treatments which target non-CD8-mediated recall alloimmunity.