Reviews & Analysis

Type I interferons (IFNs) have both direct and indirect effects on T cells, and can promote or inhibit their antiviral activity. As reviewed here, the outcome of type I IFN signalling in T cells largely depends on the timing of the signal relative to T cell receptor activation.

Regulation of the immune response in the female reproductive tract by sex hormones enables optimal conditions for fertilization and pregnancy according to the stage of the menstrual cycle, but can simultaneously affect susceptibility to pathogen infection.

A recently identified family of molecules that bind nectin and nectin-like proteins is proving to be important in the regulation of natural killer cell functions. As reviewed here, increased understanding of the activity and signalling pathways of these proteins implicates them as potential targets for the treatment of cancer, autoimmunity and viral infection.

To play their part in the generation of effective adaptive immune responses, different types of antigen-presenting cell (APC) take up and process antigen in different ways. The length of time that peptide–MHC class II complexes are present on APC surfaces can also vary depending on the cell type. This Review describes the different modes and mechanisms that regulate MHC class II processing and presentation.

In this Review, the authors describe the recent advances in the molecular regulation of germinal centre development that are also important for human B cell lymphomagenesis. They summarize the genetic alterations leading to dysregulated pathways that are important for the germinal centre reaction.

The terminal differentiation of antibody-secreting cells is controlled by a network of antagonistic transcription factors and, although it is highly complex, this process can be explained by a simple probabilistic differentiation process.

New insights into the heterogeneity of memory B cells can aid our mechanistic understanding of the longevity of humoral memory and its rapid and robust responsiveness.

The germinal centre (GC) reaction is a highly complex and regulated process. As described in this Review, recent studies have revealed dynamic cellular states in the GC, the requirements for selection of B cells that express high-affinity antibodies and the recirculation of B cells between zones of the GC.

Type I interferons have multiple direct and indirect effects on immune cells during infectious diseases. For the most part, they protect the host against infection, but they can also have adverse effects on the host. The existence of complex cross-regulatory networks involving type I interferons helps to ensure host protection with minimum host damage.

In addition to avoiding immune attack in the primary tumour, metastatic cancer cells can harness suppressive immune cells to help promote and protect them from immune surveillance as they travel from the primary tumour site, through blood or lymphatic vessels, to the metastatic site. Thus, targeting pro-metastatic immune cells may offer new therapeutic strategies for treating the major cause of death from cancer — metastatic disease.

The accumulation of cholesterol in macrophages and other immune cells promotes inflammatory responses. Inflammation, in turn, reduces the normal physiological excretion of cholesterol, which amplifies the inflammatory response and promotes myelopoiesis. Here, the authors detail the mechanisms by which cholesterol accumulation affects immune signalling pathways and highlight potential therapeutic interventions that may have benefits for metabolic diseases.

This Review describes the immune responses that occur in the heart, explaining how different innate and adaptive immune cell populations can have beneficial or detrimental roles during cardiac tissue injury. In particular, the authors focus on the unique macrophage subsets that are found in the heart and their roles in regenerating damaged cardiac tissue.