Volume 17 Issue 1, January 2016

Gomez Perdiguero and Geissmann discuss the origin of tissue macrophages as a layered system composed of resident macrophages originating mostly from yolk-sac progenitor cells and transitory myeloid cells that originate and renew from bone marrow hematopoietic stem cells.

Macrophages are essential components of mammalian tissues. In this Review, Okabe and Medzhitov discuss the emerging views of macrophage biology from evolutionary, developmental and homeostatic perspectives.

In addition to their role in systemic innate immunity, macrophages have important tissue-specific roles. In this Review, Jung and colleagues discuss how differentiation and tissue-specific activation of macrophages are regulated.

Glass and Natoli review recent advances in the understanding of mechanisms underlying priming and signal-dependent activation of macrophages, and discuss the impact of genetic variation on these processes.

Ginhoux and colleagues discuss how recent advances in macrophage development and functional diversity indicate a multidimensional concept of macrophage ontogeny, activation and function.

Low availability of glucose in tumors negatively affects the activity of tumor-infiltrating T cells. Loss of T cell function under these conditions is mediated by the microRNAs miR-101 and miR-26a, which target expression of the methytransferase EZH2 and thereby diminish the expression of anti-tumor cytokines.

Immune responses are characterized by the concerted actions of both effector mechanisms and regulatory mechanisms. Signaling via the transcription factor STAT1 downstream of receptors for interferons and interleukin 27 (IL-27) can suppress type 2 immune responses induced by group 2 innate lymphoid cells (ILCs).

Understanding cytotoxic T cells has been a major focus of immunology research for decades. Proteomic profiling of these cells now brings them into unprecedented and revealing focus.

The mechanisms that regulate the tissue-specific localization and functions of innate lymphoid cells are poorly understood. Xiong and colleagues find that CCR10⁺ innate lymphoid cells are selectively programmed in skin-draining lymph nodes for cutaneous homeostatic regulation.

Memory T_H2 cells are rapidly recruited to tissues after exposure to stimulatory ligands. McKenzie and colleagues demonstrate that ILC2s have an essential role in facilitating T_H2 cell memory responses in lung, skin and gut.

Dysregulation of group 2 innate lymphoid cells has been linked to virus-induced asthma. Fritz and colleagues demonstrate that deficiency in signaling via type I interferons in these cells can lead to dysregulated type 2 immunity during respiratory viral infection.

The signals that negatively regulate group 2 innate lymphoid cells are incompletely understood. Moro and colleagues show that interferons and IL-27 restrain the function and proliferation of these cells in vitro and in vivo through a mechanism dependent on the transcription factor STAT1.

The TCR-peptide-MHC interface is composed of conserved and diverse regions, but the relative contributions of each in shaping T cell recognition remain unclear. Garcia and colleagues show consistent germline interactions between TCR and MHC, but enough flexibility in the TCR-peptide-MHC interface to allow adjustment for different peptides.

Glucose availability is limiting in tumor environments. Zou and colleagues show that reduced glycolytic metabolism in T cells within tumors suppresses expression of the methyltransferase EZH2, which limits production of antitumor effector molecules and enhances T cell apoptosis.

Proteomic profiling can provide new insight into the cellular regulation of effector functions. Cantrell and colleagues report discordant mRNA profiles and protein profiles in activated CD8⁺ T cells and reveal new roles for mTORC1 in regulating the function of cytotoxic T lymphocytes.