The ins and outs of innate and adaptive type 2 immunity

Type 2 immunity is orchestrated by a canonical group of cytokines primarily produced by innate lymphoid cells, group 2, and their adaptive counterparts, CD4+ helper type 2 cells, and elaborated by myeloid cells and antibodies that accumulate in response. Here, we review the cytokine and cellular circuits that mediate type 2 immunity. Building from insights in cytokine evolution, we propose that innate type 2 immunity evolved to monitor the status of microbe-rich epithelial barriers (outside) and sterile parenchymal borders (inside) to meet the functional demands of local tissue, and, when necessary, to relay information to the adaptive im-mune system to reinforce demarcating borders to sustain these efforts. Allergic pathology likely results from deviations in local sustaining units caused by alterations imposed by environmental effects during post-natal developmental windows and exacerbated by mutations that increase vulnerabilities. This framework positions T2 immunity as central to sustaining tissue repair and regeneration and provides a context toward understanding allergic disease.