PI3Kγ in B cells promotes antibody responses and generation of antibody-secreting cells.

The differentiation of naive and memory B cells into antibody-secreting cells (ASCs) is a key feature of adaptive immunity. The requirement for phosphoinositide 3-kinase-delta (PI3Kδ) to support B cell biology has been investigated intensively; however, specific functions of the related phosphoinositide 3-kinase-gamma (PI3Kγ) complex in B lineage cells have not. In the present study, we report that PI3Kγ promotes robust antibody responses induced by T cell-dependent antigens.

Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine-associated myocarditis.

Rare immune-mediated cardiac tissue inflammation can occur after vaccination, including after SARS-CoV-2 mRNA vaccines. However, the underlying immune cellular and molecular mechanisms driving this pathology remain poorly understood. Here, we investigated a cohort of patients who developed myocarditis and/or pericarditis with elevated troponin, B-type natriuretic peptide, and C-reactive protein levels as well as cardiac imaging abnormalities shortly after SARS-CoV-2 mRNA vaccination.

It's the data, stupid: Inflection point for Artificial Intelligence in Indian healthcare.

Indian healthcare is fast growing and with significant chunk of it being in small, fragmented, informal sector; Artificial Intelligence (AI) is pegged as a magical tool for a better healthcare system. There is an inclination to merely mimic the US approach in the on-going policy making and legislative exercises, which can have serious fallouts for Indian healthcare. India needs a different approach to suite her unique requirements.

Maximizing insights from monogenic immune disorders.

Monogenic immune disorders provide unprecedented insights into the consequences of disrupting single genes in humans, thereby informing our understanding of fundamental immune function and disease. Genomics has accelerated monogenic disease discovery while also revealing the complexity of human disease, where several factors beyond the genome can govern pathogenesis. At this juncture, the optimal path forward will focus on maximizing basic and translational immunology insights from these disorders.

Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV-2 infection. We profiled MIS-C, adult COVID-19, and healthy pediatric and adult individuals using single-cell RNA sequencing, flow cytometry, antigen receptor repertoire analysis, and unbiased serum proteomics, which collectively identified a signature in MIS-C patients that correlated with disease severity. Despite having no evidence of active infection, MIS-C patients had elevated S100A-family alarmins and decreased antigen presentation signatures, indicative of myeloid dysfunction.

Post-infectious inflammatory disease in MIS-C features elevated cytotoxicity signatures and autoreactivity that correlates with severity.

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV2 infection in otherwise healthy children. Here, we define immune abnormalities in MIS-C compared to adult COVID-19 and pediatric/adult healthy controls using single-cell RNA sequencing, antigen receptor repertoire analysis, unbiased serum proteomics, and assays. Despite no evidence of active infection, we uncover elevated S100A-family alarmins in myeloid cells and marked enrichment of serum proteins that map to myeloid cells and pathways including cytokines, complement/coagulation, and fluid shear stress in MIS-C patients.

The Mystery of MIS-C Post-SARS-CoV-2 Infection.

Following emergence of the coronavirus disease 2019 (COVID-19) pandemic, a surge in the life-threatening illness now termed 'multisystem inflammatory syndrome in children' (MIS-C) has raised questions about the unique effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents. Two important new studies by Consiglio et al. and Gruber et al.

YAP Is Essential for Treg-Mediated Suppression of Antitumor Immunity.

Regulatory T cells (Treg) are critical for maintaining self-tolerance and immune homeostasis, but their suppressive function can impede effective antitumor immune responses. FOXP3 is a transcription factor expressed in Tregs that is required for their function. However, the pathways and microenvironmental cues governing FOXP3 expression and Treg function are not completely understood.