Gain-of-function variants in the gene encoding NLRP3 lead to constitutive inflammasome activation and excessive IL-1β production. In this resource, authors perform functional screening of clinically relevant NLRP3 variants. Structural analysis suggested multiple mechanisms by which variants activate NLRP3 and the identification of pathogenic variants that can sensitize the activation of NLRP3 in response to nigericin and cold temperature exposure.

Lu and colleagues show that signaling through the lactate receptor HCAR1 in colorectal tumor cells promotes the recruitment of immunosuppressive CCR2⁺ PMN-MDSCs and that inhibition of HCAR1 by reserpine augments the CD8⁺ T cell-mediated antitumor immune response.

The authors show that terminally differentiated colonic T_reg cells are required for maintaining colonic health and, although these cells are major producers of this cytokine, IL-10 is dispensable for their suppressive function.

Here the authors identify a nuclear short form of IL-18 in cancer cells that can enhance NK cell activation to promote tumor elimination.

Gain-of-function variants in the gene encoding NLRP3 lead to constitutive inflammasome activation and excessive IL-1β production. In this resource, authors perform functional screening of clinically relevant NLRP3 variants. Structural analysis suggested multiple mechanisms by which variants activate NLRP3 and the identification of pathogenic variants that can sensitize the activation of NLRP3 in response to nigericin and cold temperature exposure.

Lu and colleagues show that signaling through the lactate receptor HCAR1 in colorectal tumor cells promotes the recruitment of immunosuppressive CCR2⁺ PMN-MDSCs and that inhibition of HCAR1 by reserpine augments the CD8⁺ T cell-mediated antitumor immune response.

The authors show that terminally differentiated colonic T_reg cells are required for maintaining colonic health and, although these cells are major producers of this cytokine, IL-10 is dispensable for their suppressive function.

Clatworthy and colleagues examine adult nasal lymphoid tissues in response to SARS-CoV-2 infection. Longitudinal profiling reveals changes in barrier tissue to block viral entry beyond the epithelial cell layer and how tissue repair occurred after viral infection.

T_FH cells that express IL-13 are associated with high-affinity IgE responses, but factors controlling their development, transcriptional programming and exact function have remained unclear. Here, Chandrakar et al. find that the transcription factor JunB is required for T_FH13 cell maintenance and that T_FH13 cells producing IL-21 drive broad germinal center responses to allergen-specific IgG and IgE.

Here the authors identify a nuclear short form of IL-18 in cancer cells that can enhance NK cell activation to promote tumor elimination.

Strategies to advance the field of neuroimmunology by embracing its complexity via inclusion of its multidisciplinary properties were discussed at a meeting in Cold Spring Harbor. Attendees proposed fostering of open communications and funding of collaborations across disciplines, and the recognition that our understanding of the neuroimmune system requires interdisciplinary science.