Focus |

Cytokines

Cytokines are chemical cues that instruct the homeostasis and function of immune cells. Whereas proinflammatory cytokines alert the immune system to the presence of potential infection or danger, unregulated cytokine production can lead to autoinflammatory disease states. Nature Immunology presents four Reviews that discuss the regulation of type I interferons, the homeostatic cytokines IL-7 and TSLP and the inflammatory cytokine IL-17, and the implications of this for therapeutic intervention, as well as dysregulation that can lead to disease.

Editorial

Cytokines have context-dependent roles that dictate their normal physiological function; however, dysregulation or chronic activation of cytokine pathways can alter tissue balance away from a return to homeostatic quiescence toward disease-associated immunopathology.

Editorial | | Nature Immunology

Reviews

Xiaoxia Li and colleagues discuss the roles of signaling via IL-17 and its receptor and the implications of this axis for human health, noting their normal protective roles directed against fungi and bacteria as well as against pathological conditions in inflammation and cancer.

Review Article | | Nature Immunology

Ziegler and Corren review the cytokine TSLP, which regulates immune cell homeostasis at mucosal barriers, its role in allergic responses and newly discovered roles in cancer.

Review Article | | Nature Immunology

The cytokine IL-7 plays essential roles in lymphocyte development. In their Review, Barata, Durum and Seddon describe IL-7’s key homeostatic functions and how its dysregulation can lead to autoinflammatory disease and cancer.

Review Article | | Nature Immunology

From the archive

Multiple cytokines in the proinflammatory IL-1 family share the co-receptor IL-1R3. Dinarello and colleagues show that a fully humanized antibody to IL-1R3 can effectively control inflammation and disease mediated not only by IL-1 but also by IL-33 and IL-36.

Article | | Nature Immunology

Nephritis is a major cause of lupus morbidity. Putterman and colleagues use single-cell RNA sequencing on human renal and skin biopsies to describe the expression landscape associated with lupus nephritis.

Resource | | Nature Immunology

PRMT arginine methyltransferases mediate post-translational modification. Takayanagi and colleagues show that a lack of PRMT5 in cells of the T cell lineage compromises their response to cytokines dependent on the common γ-chain, due to aberrant splicing of mRNA transcripts encoding the common γ-chain and its associated kinase JAK3.

Article | | Nature Immunology

Tumor cells commonly manipulate their environment to ensure their survival. Kuan and Ziegler show that breast cancer cells release IL-1α, which acts on infiltrating myeloid cells to elicit their production of TSLP. In turn, TSLP promotes the survival of TSLPR+ tumor cells by upregulating expression of the pro-survival factor Bcl-2.

Article | | Nature Immunology

Although interleukin 17 (IL-17) has modest activity on its own, it has a substantial impact in immunity through its synergistic action with other factors and its self-sustaining feedback loop. Veldhoen discusses the role of IL-17 during infections.

Review Article | | Nature Immunology

IL-1α is a ubiquitously expressed cytokine that has diverse roles in immunity and homeostasis. Di Paolo and Shayakhmetov review IL-1α's distinctive and important role in inflammation.

Review Article | | Nature Immunology

Type I and III interferons share similar antiviral properties, but there are some important distinctions. Hartmann and colleagues review the specialized functions of type III interferons, including their ability to mediate antiviral functions at barrier surfaces.

Review Article | | Nature Immunology

IL-6 has context-dependent pro- and anti-inflammatory properties and is now regarded as a prominent target for clinical intervention. Hunter and Jones discuss the effect of IL-6 on innate and adaptive immunity, and consider how the immunobiology of IL-6 may inform clinical decisions.

Review Article | | Nature Immunology