Synovial tissue myeloid dendritic cell subsets exhibit distinct tissue-niche localization and function in health and rheumatoid arthritis.

Current rheumatoid arthritis (RA) treatments do not restore immune tolerance. Investigating dendritic cell (DC) populations in human synovial tissue (ST) may reveal pathways to reinstate tolerance in RA. Using single-cell and spatial transcriptomics of ST biopsies, as well as co-culture systems, we identified condition- and niche-specific DC clusters with distinct functions.

Selective production of IL-33-neutralizing autoantibody ameliorates asthma responses and severity.

Background: Natural anti-cytokine autoantibodies can regulate homeostasis of infectious and inflammatory diseases. The anti-cytokine autoantibody profile and relevance to the pathogenesis of asthma are unknown. We aim to identify key anti-cytokine autoantibodies in asthma patients, and reveal their immunological function and clinical significance.

Monophosphoryl lipid A directly regulates Th1 cytokine production in human CD4 T-cells through Toll-like receptor 2 and 4.

Background: The monophosphoryl lipid A (MPLA) is a detoxified LPS derivative and an emerging safe immune adjuvant in human vaccine development. The adjuvant MPLA promotes antigen-presenting cell (APC) function and preferentially induces a Th1 response following vaccination. However, the mechanism by which the MPLA detoxicates and exerts its adjuvants effect on T-cell, particualrly the Th1 response is unknown.

Low-Dose Lung Radiation Therapy for COVID-19 Lung Disease: A Preclinical Efficacy Study in a Bleomycin Model of Pneumonitis.

Purpose: Low-dose whole lung radiation therapy (LDLR) has been proposed as a treatment for patients with acute respiratory distress syndrome associated with SARS-CoV-2 infection, and clinical trials are underway. There is an urgent need for preclinical evidence to justify this approach and inform dose, scheduling, and mechanisms of action.

Methods And Materials: Female C57BL/6 mice were treated with intranasal bleomycin sulfate (7.

COVID-19 and RA share an SPP1 myeloid pathway that drives PD-L1+ neutrophils and CD14+ monocytes.

We explored the potential link between chronic inflammatory arthritis and COVID-19 pathogenic and resolving macrophage pathways and their role in COVID-19 pathogenesis. We found that bronchoalveolar lavage fluid (BALF) macrophage clusters FCN1+ and FCN1+SPP1+ predominant in severe COVID-19 were transcriptionally related to synovial tissue macrophage (STM) clusters CD48hiS100A12+ and CD48+SPP1+ that drive rheumatoid arthritis (RA) synovitis. BALF macrophage cluster FABP4+ predominant in healthy lung was transcriptionally related to STM cluster TREM2+ that governs resolution of synovitis in RA remission.