Volume 17 Issue 12, December 2016

Notch signaling promotes the maintenance of lung-resident CD8⁺ memory T cells that are transcriptionally poised for rapid effector responses but have heightened expression of inhibitory receptors, suggestive of tight regulation.

Deficiency in the RASGRP1 guanine-nucleotide-exchange factor leads to a novel primary immunodeficiency with impaired activation and proliferation of T cells and B cells and defective killing by cytotoxic T cells and natural killer cells.

Gao and colleagues show that the T cell anergy–related E3 ubiquitin ligase RNF128 is a positive regulator of TBK1 activation and interferon-β production.

Boztug and colleagues identify an immunodeficient patient with a deficiency in the guanine-nucleotide-exchange factor RASGRP1. They find that human RASGRP1 is important for the function of T cells, B cells and NK cells and that it has a role in the regulation of the cytoskeleton.

Knapp and colleagues show that elevated heme levels following hemolysis impair the control of bacterial proliferation by inhibiting phagocytosis and migration of human and mouse phagocytes independently of heme-iron acquisition by bacteria as a source of nutrients.

Alveolar macrophages help maintain lung-tissue homeostasis despite constant microbial exposure. Zhang and colleagues show that the E3 ligase TRIM29 suppresses excessive proinflammatory responses by targeting the adaptor NEMO in alveolar macrophages.

Type 2 responses can be elicited by ILC2s and T_H2 cells. Locksley and colleagues show that the epithelium-derived cytokines IL-25, IL-33 and TSLP are required for full effector activation of poised ILC2 and primed T_H2 cell populations.

Fibroblastic reticular cells influence the function of lymphocytes in secondary lymphoid organs. Ludewig and colleagues demonstrate that they also specifically restrain the activation of group 1 innate lymphoid cells in the presence of microbial stimulation to prevent immunopathology.

Microglia are CNS-resident macrophages, but studying their functions in health and disease has been challenging due to a lack of specific markers. Greter and colleagues identify the transcription factor Sall1 as being uniquely associated with microglia in the CNS, where it is important for defining their fate and homeostatic function.

The cytokine IL-18 can drive autoantibody production. Karlsson and colleagues show that such responses are limited by a three-way cellular interaction whereby splenic neutrophils activate both B cells and invariant natural killer T cells but the activated B cells are killed by FasL⁺ invariant natural killer T cells.

The CD4-versus-CD8 lineage ‘choice’ is a critical stage of thymocyte development. Singer and colleagues reveal that CD8 positive selection occurs in a defined time window and involves a compensatory mechanism that dynamically adjusts to TCR and cytokine signals.

The identity and lineage potential of the embryonic thymus-seeding progenitors that first seed the embryonic thymic rudiment is unclear. Jacobsen and colleagues find that these cells do not include multipotent stem cells or T cell–restricted progenitors but instead are lympho-myeloid progenitors.

Follicular regulatory T cells (T_FR cells) inhibit follicular helper T cell (T_FH cell)-mediated antibody production. Sharpe and colleagues show that T_FR cells induce a distinct suppressive state in T_FH cells and B cells that can be reversed by the cytokine IL-21.

T follicular helper (T_FH) cells are important for the formation of germinal centers and antibody responses. Kubo and colleagues show that T_H1 cells can induce a protective antibody response in the complete absence of T_FH cells and germinal centers.

T cells undergo metabolic reprogramming after they are activated. Rathmell and colleagues show that inflammatory Toll-like receptor signals induce glycolysis and impair the suppression of regulatory T cells, but Foxp3 can promote a switch to oxidative phosphorylation and suppression.

A goal of vaccination is to elicit and maintain tissue-resident memory T cells. Amsen and colleagues show human lung-resident memory CD8⁺ T cells express distinct transcriptional programs, including a role for Notch in cellular metabolism and maintenance.