Volume 17 Issue 6, June 2016

Single-cell transcriptome analysis has identified progenitor populations with mast-cell and eosinophil potential that are distinct from the neutrophil-monocyte lineage, segregate early in hematopoietic development and can be discriminated by expression of the transcription factor GATA-1.

Tissue-resident innate lymphoid cells (ILCs) perform diverse roles in regulating mucosal homeostasis and inflammation. The transdifferentiation of ILC2s into interferon-γ (IFN-γ)-producing ILC1-like cells generates a highly inflammatory immune cell.

Nutrient transport is regulated by signaling pathways that together indicate metabolic checkpoints in T cell self-renewal, differentiation and proliferation.

The transcription factors Tcf1 and Lef1 have intrinsic histone-deacetylase activity that is required for the repression of CD4⁺ T cell–lineage genes in CD8⁺ T cells.

Whole-body metabolism can affect immune-cell function and vice versa. Turka and colleagues review the unique metabolic properties of T_reg cells and how this relates to their function and the outcome of immune responses.

Group 1 and 3 innate lymphoid cells can be functionally plastic. Humbles and colleagues find that group 2 innate lymphoid cells in the lungs also exhibit phenotypic plasticity after exposure to infectious or noxious agents.

Transdifferentiation between group 1 and group 3 innate lymphoid cells (ILCs) has been observed in the gut. Spits and colleagues now show lung ILC2s are able to convert into ILC1s in an IL-12-dependent manner.

Cytokines of the IL-1 family have a range of effects on innate lymphoid cells. Liu and colleagues find that IL-1 facilitates the maturation and plasticity of group 2 innate lymphoid cells.

The cell-intrinsic pathways controlling the function of innate lymphoid cells are poorly defined. Artis and colleagues demonstrate that ILC2s selectively express arginase 1 and that this is critical for their bioenergetics, proliferation and function.

Using single-cell transcriptome profiling of pre-granulocyte-macrophage progenitor cells, Nerlov and colleagues identify an early hematopoietic lineage bifurcation that segregates mast cells, eosinophils, megakaryocytes and erythroid cells from monocytes, neutrophils and lymphocytes.

Moore and colleagues show that Mycobacterium tuberculosis induces miR-33 and miR-33* in macrophages to inhibit integrated pathways involved in autophagy, lysosomal function and fatty acid oxidation, and to support bacterial replication.

The aryl hydrocarbon receptor (AHR) has well-described roles in the differentiation of T cells; however, less is known about its function in innate immunity. Takaoka and colleagues demonstrate how an AHR-dependent pathway reins in production of type I interferon.

Xue and colleagues show that the transcription factors Tcf1 and Lef1 suppress CD4⁺ T lineage genes in CD8⁺ T cells through intrinsic histone deacetylase (HDAC) activity.

Asymmetric division can generate effector and memory CD8⁺ T cell precursors. Powell and colleagues show asymmetric partitioning of mTORC1 activity upon CD8⁺ T cell division, which results in distinct metabolic programming of daughter T cells.

Intracellular proteins are regulated by multiple post-translation modifications. Cantrell and colleagues show that nutrient flux regulates intracellular protein modification by O-GlcNAcylation, which drives thymocyte development and T cell proliferation.

The thymus produces γδ T cell subsets making either IFN-γ or IL-17. Silva-Santos and colleagues show that TCR signal strength within specific developmental windows is a major determinant of the generation of these γδ T cell subsets.

Invariant natural killer T cells recognize lipid antigens presented by CD1d molecules and are capable of copious cytokine production. Kronenberg and colleagues show that distinct transcriptional and epigenetic profiles can be ascribed to the NKT1, NKT2 and NKT17 subsets of these cells.