Trained immunity, tolerance, priming and differentiation: distinct immunological processes

The similarities and differences between trained immunity and other immune processes are the subject of intense interrogation. Therefore, a consensus on the definition of trained immunity in both in vitro and in vivo settings, as well as in experimental models and human subjects, is necessary for advancing this field of research. Here we aim to establish a common framework that describes the experimental standards for defining trained immunity.

Learn more

Warp Speed Ahead! Technology-Driven Breakthroughs in Skin Immunity and Inflammatory Disease

The skin’s physical barrier is reinforced by an arsenal of immune cells that actively patrol the tissue and respond swiftly to penetrating microbes, noxious agents, and injurious stimuli. When unchecked, these same immune cells drive diseases such as psoriasis, atopic dermatitis, and alopecia. Rapidly advancing microscopy, animal modeling, and genomic and computational technologies have illuminated the complexity of the cutaneous immune cells and their functions in maintaining skin health and driving diseases. Here, we discuss the recent technology-driven breakthroughs that have transformed our understanding of skin immunity and highlight burgeoning areas that hold great promise for future discoveries.

Learn more

Deciphering the regulatory landscape of fetal and adult γδ T-cell development at single-cell resolution

Sagar et al. DOI: 10.15252/embj.2019104159

γδ T cells with distinct properties develop in the embryonic and adult thymus and have been identified as critical players in a broad range of infections, antitumor surveillance, autoimmune diseases, and tissue homeostasis. Despite their potential value for immunotherapy, differentiation of γδ T cells in the thymus is incompletely understood. Here, we establish a high-resolution map of γδ T-cell differentiation from the fetal and adult thymus using single-cell RNA sequencing. We reveal novel sub-types of immature and mature γδ T cells and identify an unpolarized thymic population which is expanded in the blood and lymph nodes. Our detailed comparative analysis reveals remarkable similarities between the gene networks active during fetal and adult γδ T-cell differentiation. By performing a combined single-cell analysis of Sox13, Maf, and Rorc knockout mice, we demonstrate sequential activation of these factors during IL-17-producing γδ T-cell (γδT17) differentiation. These findings substantially expand our understanding of γδ T-cell ontogeny in fetal and adult life. Our experimental and computational strategy provides a blueprint for comparing immune cell differentiation across developmental stages.

Learn more