CD8 T SQa-1shing transplant rejection.

MHC-E restricted CD8 regulatory T cells have a restricted TCR repertoire and eliminate pathogenic CD4 T cells to mediate immune responses.

Separation anxiety: Splitting PD-L1 from CD80 suppresses autoimmunity.

A monoclonal antibody targeting CD80 on antigen presenting cells disrupts cis-interactions with PD-L1, reviving T cell inhibitory checkpoint signaling to suppress autoimmunity.

KIRCD8 T cells suppress pathogenic T cells and are active in autoimmune diseases and COVID-19.

In this work, we find that CD8 T cells expressing inhibitory killer cell immunoglobulin-like receptors (KIRs) are the human equivalent of Ly49CD8 regulatory T cells in mice and are increased in the blood and inflamed tissues of patients with a variety of autoimmune diseases. Moreover, these CD8 T cells efficiently eliminated pathogenic gliadin-specific CD4 T cells from the leukocytes of celiac disease patients in vitro. We also find elevated levels of KIRCD8 T cells, but not CD4 regulatory T cells, in COVID-19 patients, correlating with disease severity and vasculitis.

Tissue-selective alternate promoters guide NLRP6 expression.

The pryin domain (PYD) domain is involved in protein interactions that lead to assembly of immune-sensing complexes such as inflammasomes. The repertoire of PYD-containing genes expressed by a cell type arms tissues with responses against a range of stimuli. The transcriptional regulation of the PYD gene family however is incompletely understood.

Hierarchical regulation of wound healing by NOD-like receptors in cardiovascular disease.

Significance: Persistent nonmicrobial tissue injury leads to the nonlinear activation of integrated wound-healing pathways. In chronic cardiovascular diseases, local tissue undergoes dynamic remodeling involving both structural cells and professional innate immune cells in attempts to limit burden of injury. While the final effector mechanisms by which these different cellular populations participate in wound healing are functionally distinct, their upstream molecular signaling pathways can often be shared.

Mitochondrial NLRP3 protein induces reactive oxygen species to promote Smad protein signaling and fibrosis independent from the inflammasome.

Nucleotide-binding domain and leucine-rich repeat containing PYD-3 (NLRP3) is a pattern recognition receptor that is implicated in the pathogenesis of inflammation and chronic diseases. Although much is known regarding the NLRP3 inflammasome that regulates proinflammatory cytokine production in innate immune cells, the role of NLRP3 in non-professional immune cells is unclear. Here we report that NLRP3 is expressed in cardiac fibroblasts and increased during TGFβ stimulation.

Inflammasome-independent NLRP3 augments TGF-β signaling in kidney epithelium.

Tubulointerstitial inflammation and fibrosis are strongly associated with the outcome of chronic kidney disease. We recently demonstrated that the NOD-like receptor, pyrin domain containing-3 (NLRP3) contributes to renal inflammation, injury, and fibrosis following unilateral ureteric obstruction in mice. NLRP3 expression in renal tubular epithelial cells (TECs) was found to be an important component of experimental disease pathogenesis, although the biology of NLRP3 in epithelial cells is unknown.

The Nlrp3 inflammasome promotes myocardial dysfunction in structural cardiomyopathy through interleukin-1β.

Heart failure is associated with a low-grade and chronic cardiac inflammation that impairs function; however, the mechanisms by which this sterile inflammation occurs in structural heart disease remain poorly defined. Cardiac-specific heterozygous overexpression of the calcineurin transgene (CNTg) in mice results in cardiac hypertrophy, inflammation, apoptosis and ventricular dilatation. We hypothesized that activation of the Nlrp3 inflammasome, an intracellular danger-sensing pathway required for processing the pro-inflammatory cytokine interleukin-1β (IL-1β), may contribute to myocardial dysfunction and disease progression.