Techniques and analytic workflow for spatial transcriptomics and its application to allergy and inflammation.

Spatial profiling, through single-cell gene-level expression data paired with cell localization, offers unprecedented biologic insights within the intact spatial context of cells in healthy and diseased tissue, adding a novel dimension to data interpretation. This review summarizes recent developments in this field, its application to allergy and inflammation, and recent single-cell resolution platforms designed for spatial transcriptomics with a focus on data processing and analyses for efficient biologic interpretation of data. By preserving spatial context, these technologies provide critical insights into tissue architecture and cellular interactions that are unattainable with traditional transcriptomics methods, such as revealing localized inflammatory cell network in atopic dermatitis and T-cell interactions in the lung in chronic obstructive pulmonary disease.

Keratin 16 spatially inhibits type I interferon responses in stressed skin.

The stress-induced keratin intermediate filament gene/protein (K16) is spatially restricted to the suprabasal compartment of the epidermis and extensively used as a biomarker for psoriasis, hidradenitis suppurativa, atopic dermatitis and other inflammatory disorders. However, its role in these conditions remains poorly defined. Here we show that K16 negatively regulates type-I interferon (IFN) signaling and innate immune responses.

FABIO: TWAS fine-mapping to prioritize causal genes for binary traits.

Transcriptome-wide association studies (TWAS) have emerged as a powerful tool for identifying gene-trait associations by integrating gene expression mapping studies with genome-wide association studies (GWAS). While most existing TWAS approaches focus on marginal analyses through examining one gene at a time, recent developments in TWAS fine-mapping methods enable the joint modeling of multiple genes to refine the identification of potentially causal ones. However, these fine-mapping methods have primarily focused on modeling quantitative traits and examining local genomic regions, leading to potentially suboptimal performance.

Rapid response of lichen planus to baricitinib associated with suppression of cytotoxic CXCL13+CD8+ T cells.

BACKGROUNDCutaneous lichen planus (LP) is a recalcitrant, difficult-to-treat, inflammatory skin disease characterized by pruritic, flat-topped, violaceous papules on the skin. Baricitinib is an oral Janus kinase (JAK) 1/2 inhibitor that interrupts the signaling pathway of IFN-γ, a cytokine implicated in the pathogenesis of LP.METHODSIn this phase II trial, 12 patients with cutaneous LP received 2 mg daily baricitinib for 16 weeks, accompanied by in-depth spatial, single-cell, and bulk transcriptomic profiling of pre- and posttreatment samples.

The STAT3/SETDB2 axis dictates NF-κB-mediated inflammation in macrophages during wound repair.

Macrophage transition from an inflammatory to reparative phenotype after tissue injury is controlled by epigenetic enzymes that regulate inflammatory gene expression. We have previously identified that the histone methyltransferase SETDB2 in macrophages drives tissue repair by repressing NF-κB-mediated inflammation. Complementary ATAC-Seq and RNA-Seq of wound macrophages isolated from mice deficient in SETDB2 in myeloid cells revealed that SETDB2 suppresses the inflammatory gene program by inhibiting chromatin accessibility at NF-κB-dependent gene promoters.