Cellular pathways and molecular events that shape autoantibody production in COVID-19.

A hallmark of COVID-19 is the variety of complications that follow SARS-CoV-2 infection in some patients, and that target multiple organs and tissues. Also remarkable are the associations with several auto-inflammatory disorders and the presence of autoantibodies directed to a vast array of antigens. The processes underlying autoantibody production in COVID-19 have not been completed deciphered.

Swaying the advantage: multifaceted functions of inflammasomes in adaptive immunity.

Eukaryotic cells are equipped with cytoplasmic sensors that recognize diverse pathogen- or danger-associated molecular patterns. In cells of the myeloid lineage, activation of these sensors leads to the assembly of a multimeric protein complex, called the inflammasome, that culminates in the production of inflammatory cytokines and pyroptosis. Recently, investigation of the inflammasomes in lymphocytes led to the discovery of functional pathways that were initially believed to be confined to the innate arm of the immune system.

Inflammasome functional activities in B lymphocytes.

Studies in animal models and human subjects have shown that, in addition to their implication in innate immunity, inflammasomes also can play a role in adaptive immunity. However, the contribution of the nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome pathway to adaptive immunity remains incompletely explored. Here, we show that NLRP3 plays an important role in different facets of B cell functions, including proliferation, antibody production, and secretion of inflammatory and anti-inflammatory cytokines.

Engineered immune cells as therapeutics for autoimmune diseases.

Current treatment options for autoimmune disease (AID) are essentially immunosuppressive, inhibiting the inflammatory cascade, without curing the disease. Therapeutic monoclonal antibodies (mAbs) that target B cells showed efficacy, emphasizing the importance of B lymphocytes in autoimmune pathogenesis. Treatments that eliminate more potently B cells would open a new therapeutic era for AID.

Pharmacological and Electroceutical Targeting of the Cholinergic Anti-Inflammatory Pathway in Autoimmune Diseases.

Continuous dialogue between the immune system and the brain plays a key homeostatic role in various immune responses to environmental cues. Several functions are under the control of the vagus nerve-based inflammatory reflex, a physiological mechanism through which nerve signals regulate immune functions. In the cholinergic anti-inflammatory pathway, the vagus nerve, its pivotal neurotransmitter acetylcholine, together with the corresponding receptors play a key role in modulating the immune response of mammals.