Inhibition of vascular smooth muscle cell PERK/ATF4 ER stress signaling protects against abdominal aortic aneurysms.

Abdominal aortic aneurysms (AAA) are a life-threatening cardiovascular disease for which there is a lack of effective therapy preventing aortic rupture. During AAA formation, pathological vascular remodeling is driven by vascular smooth muscle cell (VSMC) dysfunction and apoptosis, for which the mechanisms regulating loss of VSMCs within the aortic wall remain poorly defined. Using single-cell RNA-Seq of human AAA tissues, we identified increased activation of the endoplasmic reticulum stress response pathway, PERK/eIF2α/ATF4, in aortic VSMCs resulting in upregulation of an apoptotic cellular response.

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.

Topical Mupirocin Treatment Reduces Interferon and Myeloid Signatures in Cutaneous Lupus Erythematous Lesions Through Targeting of Staphyloccal Species.

Objective: Cutaneous lupus erythematosus (CLE) is an inflammatory skin manifestation of systemic lupus erythematosus. Type I interferons (IFNs) promote inflammatory responses and are elevated in CLE lesions. We recently reported that CLE lesions are frequently colonized with Staphylococcus aureus.

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.