This month's Focus features four specially commissioned Reviews on cytokines in the balance between health and disease, and the implications for targeting specific cytokines for therapeutic intervention.

See https://www.nature.com/collections/cytokines.

Gaudenzio and colleagues show that house dust mite extracts directly activate TRPV1+ sensory neurons, which drive the development of allergic skin inflammation by inducing the degranulation of mast cells through release of the neuropeptide substance P.

See Serhan et al.

A20, encoded by TNFAIP3, is a negative-feedback inhibitor of NF-κB. Grey and colleagues identify natural human variants of TNFAIP3 that lower A20 activity and increase autoinflammatory responses. These alleles were inherited by descendants of Denisovans who crossed the Wallace line to inhabit Oceania.

See Zammit et al.

Inflammatory signals activate hematopoietic stem and progenitor cells to rapidly boost myelopoiesis. Aifantis and colleagues identify the E3 ubiquitin ligase SPOP as a negative regulator of 'emergency hematopoiesis' in such cells in the bone marrow.

See Aifantis et al.

Cella, Gamini and colleagues show that human mucosal tissues contain a spectrum of innate lymphoid cells (ILCs). ILCs span from ILC3 to ILC1, with subsets having intermediate features of both.

See Colonna et al.

This month's Focus features a series of specially commissioned Reviews that discuss the metabolic and molecular mechanisms that allow immune cells and hematopoietic progenitor cells to adapt to diverse pathophysiological conditions or environments.

See: https://www.nature.com/collections/adaptation.

The original online version of the cover image contained a typographical error. This has now been corrected.

Adult pancreatic β-cells are quiescent. Qi and colleagues show that mice lacking the receptors TLR2 and TLR4 exhibit islet-mass expansion during diet-induced obesity, due to β-cell proliferation in a manner dependent on the kinase ERK.

See Qi et al.

Lymph fluid carries cells, debris and viruses to draining lymph nodes (LNs). Hickman and colleagues show that large viruses can enter LN conduits and gain access to dendritic cells that are positioned deep within LNs for efficient antigen presentation to CD8+ T cells.

See Hickman et al.

Shulman and colleagues show that in Peyer’s patches, in contrast to lymph nodes and spleen, T cells predominantly promoted expansion of B cells without clonal selection during pre-germinal centre events.

See Shulman et al.

Koning and colleagues used mass cytometry, single-cell RNA-seq and high-throughput TCR sequencing to characterize the CD4+ T cell compartment in the human fetal intestine.

See Koning et al.

Fan and colleagues show that the circular RNA circPan3 controls expression of the cytokine receptor IL-13Rα1 on intestinal stem cells and, thus, the renewal of those cells in response to IL-13 derived from group 2 innate lymphoid cells.

See Fan et al.

Macrophages promote both injury and repair following myocardial infarction, but discriminating functions within mixed populations remains challenging. Epelman and colleagues use fate mapping and single-cell transcriptomics to describe the dynamics of resident and recruited cardiac macrophages during ischemic injury.

See Dick et al.