Volume 17 Issue 7, July 2016

Perivascular and subdural meningeal macrophages at the interface between the central nervous system and the periphery are self-renewing and arise from early embryonic precursors. Macrophages residing in the choroid plexus have dual origin, developing from circulating bone-marrow-derived monocytes and embryonic progenitors.

B cell and T cell memory differentiation requires the transcription factor Bach2, which inhibits the effector-cell fate by limiting antigen-receptor-stimulation-induced gene expression and restricting premature expression of the transcriptional regulator Blimp-1.

In natural killer (NK) cells, CIS restrains a signaling pathway elicited by interleukin 15 (IL-15) that leads to activation of the kinase JAK1. Removal of CIS from NK cells increases their capacity to reduce the metastatic dissemination of breast cancer and melanoma in mice.

Innate lymphoid cells serve multiple roles in maintaining tissue homeostasis and responding to tissue insults and can contribute to chronic inflammatory diseases.

Targeting innate lymphoid cells, the innate counterparts of T cells, might help direct an appropriate immune response during preventive and therapeutic strategies aimed at pathogens and inflammatory pathologies

NK cells and ILC1s are developmentally distinct but share many functional similarities. Spits and colleagues describe current knowledge on the biology of these cells and the conditions under which they can be distinguished.

In this Review, Klose and Artis focus on how group 2 ILC and group 3 ILC responses are regulated and how they interact with other immune and non-immune cells to mediate their functions.

Innate lymphoid cells (ILCs) arise from distinct hematopoietic progenitors. Zook & Kee discuss the transcriptional programs that direct the development of natural killer cells and various ILC subsets.

The redundant or specialized roles of innate lymphoid cells (ILCs) relative to those of T cells in vivo remain hard to delineate experimentally. Bando and Colonna review the current understanding of the specialized in vivo functions of ILCs and discuss the genetic mouse models used to assess the contributions of ILCs versus those of T cells.

The appearance of innate lymphoid cells was a major step in the evolution of vertebrate immunity. In their Perspective, Vivier et al. survey these cells in evolution and their functional inter-relationship with conventional T cells and B cells.

Microglia progenitors seed the central nervous system from the yolk sac, but little is known about the origin of non-parenchymal macrophages. Prinz and colleagues demonstrate that these macrophages in the central nervous system are related to but distinct from microglia and are largely of embryonic origin.

The DNA methyltransferase Dnmt3a has not been studied in innate immunity. Cao and colleagues show that Dnmt3a enhances antiviral responses via a non-canonical mechanism to activate the kinase TBK1 and the production of type I interferons in macrophages.

IL-15-driven NK cells mediate anti-tumor immunity, but how IL-15 is negatively regulated remains unclear. Huntington and colleagues find that CIS, a member of the suppressor of cytokine signaling family, suppresses the response to IL-15 and, as a result, CIS-deficient mice are more resistant to cancer metastasis.

Signaling via the inducible costimulator ICOS drives the stepwise development of follicular helper T cells. Kong and colleagues describe an ICOS–kinase TBK1 signaling pathway that specifies the commitment of these cells.

Activation of CD4⁺ T cells leads to their polarization to various effector states. Goldrath and colleagues identify a role for the E-protein inhibitor Id2 in promoting T_H1 cell polarization over T_FH cell polarization. Reciprocally, the transcription factor Bcl-6 represses Id2 expression in T_FH cells.

Davis and colleagues show that cholesterol sulfate, a naturally occurring analog of cholesterol, regulates CD3ζ phosphorylation and thymic selection.

T cell activation upon TCR signaling can lead to development of effector and memory cells. Roychoudhuri and colleagues show that the transcription factor BACH2 promotes memory CD8⁺ T cell generation by blocking access to genomic regulatory sites recognized by AP-1.

T cells provide help to B cells in germinal centers. Kurosaki and colleagues show that B cells of lower affinity receive weaker T cell help. This scenario results in higher expression of the transcriptional repressor Bach2 and promotes the development of memory B cells.

B cells can capture antigen to present to helper T cells. Tolar and colleagues show that germinal center B cells use a distinct synaptic architecture to capture antigen with higher mechanical forces than those of other B cells, which might provide the basis for affinity discrimination.

Austen and colleagues assess the transcriptional profiles of mast cells isolated from peripheral connective tissues and basophils isolated from spleen and blood. Mast cells show a unique tissue profile and minimal homology with basophils or other immunocytes.