Browse Articles

Devant and Kagan review the biochemical and cell biological mechanisms that control gasdermin D pore-forming activity and its diverse downstream immunological effects.

Smith et al. present a resource detailing drivers of transcriptional heterogeneity of synovial fibroblasts cell states in the inflamed joints of human patients with rheumatoid arthritis.

Human leukocyte antigen (HLA)-E binds epitopes derived from HLA-A, HLA-B, HLA-C and HLA-G signal peptides (SPs) and serves as a ligand for CD94/NKG2A and CD94/NKG2C receptors. Carrington and colleagues provide comprehensive analysis of classical HLA class I SP variants and show that these can determine CD94/NKG2–HLA-E engagement.

First Nations peoples of Australia have disproportionate rates of chronic comorbidities such as diabetes and renal disease. A study of COVID vaccination in First Nations peoples reveals that perturbed antibody responses can occur in individuals with comorbidities in a way strongly associated with altered IgG glycosylation patterns.

Indigenous populations are disproportionately affected by COVID-19, but are rarely studied. An investigation of the immune response of Australian First Nations people to SARS-CoV-2 vaccination and infection shows a major effect of comorbidities.

Choi et al. show that infiltrating CCR2⁺ monocytes, by provision of IL-6, instruct tissue-resident microglia to become ‘repair-associated microglia’ following intracerebral hemorrhage, promoting cerebrovascular repair and neurological recovery.

Kedzierska et al. report an association between low production of receptor-binding domain antibodies after mRNA vaccination and altered glycosylation of IgG before vaccination in people with comorbidities, and show that this condition disproportionately affects Australia’s First Nations peoples because of the high burden of comorbidities in this population.

The magnitude and quality of the germinal center response after vaccination decline with age. We found that T follicular helper (T_FH) cells are enriched in the dark zone of germinal centers in aged mice, which impairs the expansion of the follicular dendritic cell network upon immunization and reduces antibody responses.

Linterman and colleagues examine germinal center formation in older individuals. They find that aged T_FH cells have dysregulated CXCR4 expression, which causes spatial mislocalization of these cells in germinal centers, impairing their ability to provide help to B cells and to promote antibody production.

De Martin, Ludewig and colleagues define the topology and molecular identity of human tonsillar stromal cells and show that PI16-expressing fibroblastic reticular cells shape subepithelial niches for efficient T cell activation and differentiation.

Pikor et al. show that a set of conserved, bidirectional cues exchanged between fibroblastic reticular cells and immune cells sustain B cell niches, which control humoral immune responses across mouse and human lymphoid organs.

In mice and humans, changes in neutrophil phenotypes and functionality during aging aggravate thromboinflammation in ischemic brain injury and determine the pathology associated with strokes. In mice, inhibition of CXCL3 signaling and rejuvenation of bone marrow offer ways of restricting brain injury and improving stroke outcomes.

Bacigaluppi and colleagues report that the accumulation of atypical mature and immature neutrophil subsets and a dysregulated emergency granulopoiesis response in aged mice and humans affect the outcome of stroke.

Bedoui and colleagues describe a sequential process of integration of innate and CD40-delivered signals in APCs, which optimizes their capacity to drive antiviral CD8⁺ T cell responses.

In this Review, Künzli and Masopust provide updates on our understanding of the biology of memory CD4⁺ T cells as well as key technological advances that facilitate their characterization.