Brenner and colleagues identify two predominant tissue-resident T_reg cell subsets (suppressive CD25^hiCXCR6^pos and dysfunctional CD25^loAREG^pos) in synovial joints from patients with rheumatoid arthritis. These functionally divergent T_reg cell subsets are shaped by local microenvironmental cues supplied by macrophages or fibroblasts.

Here, the authors conduct integrated multiomics analysis of B cell activation, differentiation and diversification responses to malaria infection and provide a graphical user interface for readers to mine these data.

Some patients with pyoderma gangrenosum harbor a mutation (R57C) in OTULIN that disrupts the interaction between OTULIN and LUBAC leading to hyperactivation in monocytes and enhanced susceptibility of keratinocytes to TNF-induced, caspase-dependent cell death. One patient treated with anti-TNF therapy showed clinical remission of skin ulceration.

This study compares the humoral response of individuals who received inactivated influenza vaccines to that of individuals who received an mRNA-based quadrivalent influenza vaccine. The mRNA-based vaccine induced prolonged germinal center responses, more antibodies and increased numbers of memory B cells.

Brenner and colleagues identify two predominant tissue-resident T_reg cell subsets (suppressive CD25^hiCXCR6^pos and dysfunctional CD25^loAREG^pos) in synovial joints from patients with rheumatoid arthritis. These functionally divergent T_reg cell subsets are shaped by local microenvironmental cues supplied by macrophages or fibroblasts.

Here, the authors conduct integrated multiomics analysis of B cell activation, differentiation and diversification responses to malaria infection and provide a graphical user interface for readers to mine these data.

Some patients with pyoderma gangrenosum harbor a mutation (R57C) in OTULIN that disrupts the interaction between OTULIN and LUBAC leading to hyperactivation in monocytes and enhanced susceptibility of keratinocytes to TNF-induced, caspase-dependent cell death. One patient treated with anti-TNF therapy showed clinical remission of skin ulceration.

This study compares the humoral response of individuals who received inactivated influenza vaccines to that of individuals who received an mRNA-based quadrivalent influenza vaccine. The mRNA-based vaccine induced prolonged germinal center responses, more antibodies and increased numbers of memory B cells.

Chen and colleagues identify that baseline IFNβ levels correlate with antibody responses to inactivated influenza vaccines in humans, and show that type I IFNs, IL-12 and IL-21 functionally enhance antibody responses in human organoids.

Here the authors characterize mRNA-based tuberculosis vaccine candidates BNT164a1 and BNT164b1 and show that they are immunogenic, well tolerated and efficacious in preclinical animal models.

In a shifting regulatory landscape that increasingly favors organ-on-chip and human cell-based systems, embedding immune complexity is essential to advance new approach methodologies beyond reductionist models and toward a hybrid ecosystem that integrates animal studies.