B cells transiently increase interleukin (IL)-2 receptor expression upon activation. Gauthier et al. examine the B cell-intrinsic role of IL-2 and define an IL-2-MAF axis that promotes the differentiation of CD25+ age-associated B cells toward a regula…
Adaptive programming in lymphocytes during infection depends on when—not just whether—they sense antigen and proinflammatory cytokines such as IL-12. Grassmann et al. reveal that AP-1/STAT4 cooperation links signal timing to lymphocyte fate, tuning CD8…
Dhariwala et al. demonstrate that commensal microbes recruit classical monocytes to neonatal skin. Disrupting this interaction triggers aberrant IL-17 secretion from cutaneous T lymphocytes, heightening risk of skin inflammation. IL-1 signaling in skin…
Mapping TCRs to antigens at scale presents a major challenge. Gaglione et al. develop an approach to rapidly synthesize and screen thousands of TCRs, enabling broad TCR-antigen screening. Examining T cell specificity in vitiligo uncovers autoreactive T…
Cytosolic nucleic acid sensors contribute to pathogenic and autoinflammatory inflammation; however, little is known about the metabolic adaptations that they induce. Dunphy et al. find that these pathways induce type I interferon-dependent metabolic ch…
Tumor-associated macrophages (TAMs) enhance cancer progression by driving angiogenesis, extracellular matrix remodeling, and immune suppression, yet their impact on nerve growth is unclear. Dolci and colleagues show that TAMs directly stimulate neurite…
In cellular immunity, cytotoxic lymphocytes-derived granzyme A (GZMA) targets the pore-forming protein GSDMB in target cells to confer pyroptotic killing, but how GZMA specifically recognizes and cleaves GSDMB is unknown. Zhong et al. demonstrate that …
The incidence of colorectal cancer (CRC) is elevated in individuals with inflammatory bowel disease. Pires et al. find that the cytokine TL1A stimulates production of GM-CSF by ILC3s, which triggers emergency granulopoiesis and neutrophil recruitment a…
Commensal microbes shape host immunity at barrier tissues and promote resistance to infection. Xu et al. identify a commensal Corynebacterium-derived lipid that activates IL-17⁺ γδ T cells via T cell receptor and IL-1 signaling, enhancing barrier defen…
IL-9 is canonically associated with anti-helminth and allergic immunity. However, in this issue of Immunity, Jiang et al. and Castelli et al. demonstrate how integrating IL-9 signaling in T cells enhances their persistence and anti-tumor function in so…
