NK cell functions are tightly regulated by the balance between the inhibitory and stimulatory surface receptors. We investigated the surface expression of galectin-9 (Gal-9) and its function in NK cells from HIV-infected individuals on antiretroviral therapy, long-term nonprogressors, and progressors compared with healthy controls. We also measured the expression of TIGIT and TIM-3 on different NK cell subpopulations and compared their functionality to Gal-9+ NK cells. Our data demonstrated significant upregulation of Gal-9 on NK cells in HIV-infected groups versus healthy controls. Gal-9 expression was associated with impaired expression of cytotoxic effector molecules granzyme B, perforin, and granulysin. In contrast, Gal-9 expression significantly enhanced IFN-γ expression in NK cells of HIV-1–infected individuals. We also found an expansion of TIGIT+ NK cells in HIV-infected individuals; however, dichotomous to Gal-9+ NK cells, TIGIT+ NK cells expressed significantly higher amounts of cytotoxic molecules but lower IFN-γ. Moreover, lower expression of cytotoxic effector molecules in Gal-9+ NK cells was associated with higher CD107a expression, which suggests indiscriminate degranulation. Importantly, a positive correlation between the plasma viral load and Gal-9+ NK cells was observed in progressors. Finally, we found that a cytokine mixture (IL-12, IL-15, and IL-18) can improve effector functions of Gal-9+ NK cells in HIV-infected individuals, although, such an effect was observed for Gal-9− NK cells, as well. Overall, our data highlight the important role of Gal-9 in dysfunctional NK cells and, more importantly, a dichotomy for the role of Gal-9 versus TIGIT and suggest a potential new avenue for the development of therapeutic approaches.
Mycosis fungoides (MF) is the most prevalent type of skin lymphoma. In its early stages, it has a favorable prognosis. However, in its late stages, it is associated with an increased risk of mortality. This systematic review aimed to identify the transcriptomic changes involved in MF pathogenesis and progression. A literature search was conducted using the database PubMed, followed by the extraction of 2245 genes which were further filtered to 150 recurrent genes that appeared in two or more publications. Categorization of these genes identified activated pathways involved in pathways such as cell cycle and proliferation, chromosomal instability, and DNA repair. We identified 15 genes implicated in MF progression, which were involved in cell proliferation, immune checkpoints, resistance to apoptosis, and immune response. In highlighting the discrepancies in the way MF transcriptomic data is obtained, further research can focus on not only unifying their approach but also focus on the 150 pertinent genes identified in this review.
8 July 2022 in Journal of Cutaneous Medicine and Surgery
Background: Teledermatology utilizes photoimaging and background information to allow dermatologists to remotely provide a diagnosis to practitioners. ConsultDerm is an asynchronous, web-based teledermatology software that allows practitioners to submit their electronic referrals for assessment by board-certified dermatologists. Objective: Our study aimed to retrospectively analyze teledermatology’s utilization in Canada by using the teledermatology platform ConsultDerm. Methods: After implementing inclusion criteria, 1000 patients were selected, and relevant demographic and clinical information were extracted for data analysis. In addition, an online survey with pre-formulated questions was distributed to 7 dermatologists currently using the ConsultDerm platform to determine their experience in utilizing teledermatology. Results: Of the 1000 patients, 66.5% had not received treatment prior to their teledermatology referral, and on average, patients experienced symptoms for 489.5 days prior to their referral. Diagnoses made were categorized by conditions, most common being dermatitis (37.1%), followed by acneiform conditions (10.6%), benign lesions/neoplasms (12.1%), infections (9.4%), and dyspigmentation (3.1%). Most consults originated from small population centers, and the referring practitioners were predominantly family physicians. Dermatologists utilizing the platform expressed ease of use, however, areas of improvement were identified such as increasing the quality of imaging and more detailed patient history. Conclusion: Through our analysis of 1000 cases, we identified how a teledermatology consultation could be used to assess a wide variety of cutaneous conditions, improving access for patients who may face barriers to seeing a dermatologist.