The Cellular and Transcriptomic Early Innate Immune Response to BCG Vaccination in Mice.

It is established that BCG vaccination results in the development of both a specific immune response to mycobacterial infections and a nonspecific (heterologous) immune response, designated as trained immunity (TRIM), to other pathogens. We hypothesized that local BCG immunization may induce an early immune response in bone marrow and spleen innate immunity cells. The early transcriptomic response of various populations of innate immune cells, including monocytes, neutrophils, and natural killer (NK) cells, to BCG vaccination was examined.

Early transcriptomic response of innate immune cells to subcutaneous BCG vaccination of mice.

Objectives: Current data suggests that Bacille Calmette-Guerin (BCG) vaccination contributes to nonspecific enhancement of resistance to various infections. Thus, BCG vaccination induces both specific immunity against mycobacteria and non-specific "trained immunity" against various pathogens. To understand the fundamental mechanisms of "trained" immunity, studies of transcriptome changes occurring during BCG vaccination in innate immunity cells, as well as in their precursors, are necessary.

Non-viral-mediated gene transfer of OX40 ligand for tumor immunotherapy.

Background: Immune checkpoint blockade (ICB) is rapidly becoming a standard of care in the treatment of many cancer types. However, the subset of patients who respond to this type of therapy is limited. Another way to promote antitumoral immunity is the use of immunostimulatory molecules, such as cytokines or T cell co-stimulators.

Two modes of targeting transposable elements by piRNA pathway in human testis.

PIWI proteins and their partner small RNAs, termed piRNAs, are known to control transposable elements (TEs) in the germline. Here, we provide evidence that in humans this control is exerted in two different modes. On the one hand, production of piRNAs specifically targeting evolutionarily youngest TEs (L1HS, L1PA2-L1PA6, LTR12C, SVA) is present both at prenatal and postnatal stages of spermatogenesis and is performed without involvement of piRNA clusters.

Intragenic Locus in Human PIWIL2 Gene Shares Promoter and Enhancer Functions.

Recently, more evidence supporting common nature of promoters and enhancers has been accumulated. In this work, we present data on chromatin modifications and non-polyadenylated transcription characteristic for enhancers as well as results of in vitro luciferase reporter assays suggesting that PIWIL2 alternative promoter in exon 7 also functions as an enhancer for gene PHYHIP located 60Kb upstream. This finding of an intragenic enhancer serving as a promoter for a shorter protein isoform implies broader impact on understanding enhancer-promoter networks in regulation of gene expression.

Expression profiles of PIWIL2 short isoforms differ in testicular germ cell tumors of various differentiation subtypes.

PIWI family proteins have recently emerged as essential contributors in numerous biological processes including germ cell development, stem cell maintenance and epigenetic reprogramming. Expression of some of the family members has been shown to be elevated in tumors. In particular, PIWIL2 has been probed as a potential neoplasia biomarker in many cancers in humans.