Recent Research Publications- June 2022
Bermick JR, Issuree P, denDekker A, Gallagher KA, Kunkel S, Lukacs N, Schaller M.
Immunol Cell Biol. 2022 May 24. doi: 10.1111/imcb.12561. Epub ahead of print.
Neonatal CD4+ T cells have reduced or delayed T cell receptor (TCR) signaling responses compared to adult cells, but the mechanisms underlying this are poorly understood. This study tested the hypothesis that human neonatal naïve CD4+ TCR signaling and activation deficits are related to differences in H3K4me3 patterning and chromatin accessibility. Following initiation of TCR signaling using anti-CD3/anti-CD28 beads, adult naïve CD4+ T cells demonstrated increased CD69, phosphoCD3E and IL-2, TNF-α, IFN-γ and IL-17A compared to neonatal cells. In contrast, following TCR-independent activation using PMA/ionomycin, neonatal cells demonstrated increased expression of CD69, IL-2 and TNF- α and equivalent phosphoERK compared to adult cells. H3K4me3 ChIP-seq and ATAC-seq were performed on separate cohorts of naïve CD4+ T cells from term neonates and adults, and RNA-seq data from neonatal and adult naïve CD4+ T cells was obtained from the Blueprint Consortium. Adult cells demonstrated overall increased chromatin accessibility and a higher proportion of H3K4me3 sites associated with open chromatin and active gene transcription compared to neonatal cells. Adult cells demonstrated increased mRNA expression of the TCR-associated genes FYN, ITK, CD4, LCK and LAT, which was associated with increased H3K4me3 at the FYN and ITK gene loci and increased chromatin accessibility at the CD4, LCK and LAT loci. These findings indicate that neonatal TCR-dependent defects in activation are epigenetically regulated and provide a potentially targetable mechanism to enhance neonatal CD4+ T cell responses.
Early Diagnostics of Vulvar Intraepithelial Neoplasia
Kesić V, Vieira-Baptista P,
Cancers (Basel). 2022 Apr 4;14(7):1822. doi: 10.3390/cancers14071822.
The spectrum of vulvar lesions ranges from infective and benign dermatologic conditions to vulvar precancer and invasive cancer. Distinction based on the characteristics of vulvar lesions is often not indicative of histology. Vulvoscopy is a useful tool in the examination of vulvar pathology. It is more complex than just colposcopic examination and presumes naked eye examination accompanied by magnification, when needed. Magnification can be achieved using a magnifying glass or a colposcope and may aid the evaluation when a premalignant or malignant lesion is suspected. It is a useful tool to establish the best location for biopsies, to plan excision, and to evaluate the entire lower genital system. Combining features of vulvar lesions can help prediction of its histological nature. Clinically, there are two distinct premalignant types of vulvar intraepithelial neoplasia: HPV-related VIN, more common in young women, multifocal and multicentric; VIN associated with vulvar dermatoses, more common in older women and usually unicentric. For definite diagnosis, a biopsy is required. In practice, the decision to perform a biopsy is often delayed due to a lack of symptoms at the early stages of the neoplastic disease. Clinical evaluation of all VIN lesions should be conducted very carefully, because an underlying early invasive squamous cancer may be present.