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Chronic skin inflammatory diseases including atopic dermatitis (AD) and psoriasis have been considered uncontrolled inflammatory responses, which have usually troubled patients around the world. Moreover, the recent method to treat AD and psoriasis has been based on the inhibition, not regulation, of the abnormal inflammatory response, which can induce a number of side effects and drug resistance in long-term treatment. Mesenchymal stem/stromal cells (MSCs) and their derivatives have been widely used in immune diseases based on their regeneration, differentiation, and immunomodulation with few adverse effects, which makes MSCs a promising treatment for chronic skin inflammatory diseases. As a result, in this review, we aim to systematically discuss the therapeutic effects of various resources of MSCs, the application of preconditioning MSCs and engineering extracellular vesicles (EVs) in AD and psoriasis, and the clinical evaluation of the administration of MSCs and their derivatives, which can provide a comprehensive vision for the application of MSCs and their derivatives in future research and clinical treatment.

BackgroundTrichilemmal carcinoma (TLC) is a rare malignant cutaneous adnexal neoplasm, with no relatively comprehensive research.ObjectiveThe aim of this study is to perform an updated statistical analysis so as to better understand TLC’s epidemiology, clinical features, diagnosis, and treatment.MethodsThe diagnosis and treatment of three TLC cases in our department were summarized. Then, all TLC cases published in the literature were retrieved for a comprehensive analysis, followed by the analysis of global trends and regional distribution, demographic characteristics, clinical features, pathogenesis, histopathological features, and treatment and prognosis of TLC.ResultsOf the 231 cases, the incidence of TLC has shown an upward trend recently, especially in China, in Asia. The susceptible population is men aged 60–80 and women over 80, and the most prone location is head and neck. The phenotype of TLC is not always typical and may be misdiagnosed because of the coexistence of other diseases. There is a linear relationship between the diameter and its duration or thickness. UV, locally present skin lesions, trauma, scarring, organ transplantation, and genetic disorders may trigger the occurrence of TLC. Periodic acid–Schiff staining and CD34, but not Epithelial Membrane Antigen (EMA), were helpful in the diagnosis of TLC. Although effective, surgical excision and Mohs micrographic surgery need further improvement to reduce recurrence of TLC. Carcinoma history is an independent risk factor for TLC recurrence.LimitationsThe limitation of this study is the lack of randomized controlled trial on TLC treatment and recurrence.ConclusionTLC has the possibility of invasive growth and recurrence, especially in patients with longer duration and carcinoma history.

The long-term persistence of viral antigens drives virus-specific CD8 T cell exhaustion during chronic viral infection. Yet exhausted, CD8 T cells are still endowed with certain levels of effector function, by which they can keep viral replication in check in chronic infection. However, the regulatory factors involved in regulating the effector function of exhausted CD8 T cell are largely unknown. Using mouse model of chronic LCMV infection, we found that the deletion of transcription factor TCF-1 in LCMV-specific exhausted CD8 T cells led to the profound reduction in cytokine production and degranulation. Conversely, ectopic expression of TCF-1 or using agonist to activate TCF-1 activities promotes the effector function of exhausted CD8 T cells. Mechanistically, TCF-1 fuels the functionalities of exhausted CD8 T cells by promoting the expression of an array of key effector function-associated transcription regulators, including Foxo1, Zeb2, Id3, and Eomes. These results collectively indicate that targeting TCF-1 mediated transcriptional pathway may represent a promising immunotherapy strategy against chronic viral infections by reinvigorating the effector function of exhausted virus-specific CD8 T cells.

The combination antiretroviral therapeutic (cART) regime effectively suppresses human immunodeficiency virus (HIV) replication and prevents progression to acquired immunodeficiency diseases. However, cART is not a cure, and viral rebound will occur immediately after treatment is interrupted largely due to the long-term presence of an HIV reservoir that is composed of latently infected target cells that maintain a quiescent state or persistently produce infectious viruses. CD4 T cells that reside in B-cell follicles within lymphoid tissues, called follicular helper T cells (TFH), have been identified as a major HIV reservoir. Due to their specialized anatomical structure, HIV-specific CD8 T cells are largely insulated from this TFH reservoir. It is increasingly clear that the elimination of TFH reservoirs is a key step toward a functional cure for HIV infection. Recently, several studies have suggested that a fraction of HIV-specific CD8 T cells can differentiate into a CXCR5-expressing subset, which are able to migrate into B-cell follicles and inhibit viral replication. In this review, we discuss the differentiation and functions of this newly identified CD8 T-cell subset and propose potential strategies for purging TFH HIV reservoirs by utilizing this unique population.