Volume 19 Issue 7, July 2018

The cytokine IL-17F constrains the growth of immunoregulatory Clostridium cluster XIVa species and represents a potential therapeutic target for the treatment of inflammatory bowel disease.

Tumor-associated natural killer cells have elevated expression of the checkpoint inhibitory receptor TIGIT. Monoclonal antibody–mediated blockade targeting TIGIT unleashes the anti-tumor activity of both natural killer cells and T cells in preclinical mouse models and efficiently delays tumor growth.

Plasmacytoid dendritic cells (pDCs) are type I interferon–producing cells with antigen-presenting potential. pDC populations are composed of transcriptionally and functionally heterogeneous cellular subsets with distinct hematopoietic precursor origin.

Autoimmune disease has proven to be a unique conceptual and medical challenge, but hope for effective targeted therapies is tantalizingly close.

The thymus has a critical role in the establishment of appropriately educated and self-tolerant T cells. In their Focus Review, Cheng and Anderson discuss the most recent insights into how the thymus establishes self-tolerance.

T_reg cells have a critical role in maintaining peripheral tolerance. In this Focus Review, Dominguez-Villar and Hafler describe how the instability and plasticity of T_reg cells can contribute to the breakdown of tolerance and lead to autoimmune disease.

Autoimmune disease has been the subject of intense genetic study. In this Focus Review, Todd and colleagues describe recent advances and approaches in the genetic analysis of autoimmune disease.

The rates of autoimmune disease are rising more rapidly than can be explained by changes in genetics. In this Focus Review, Verdu and Danska describe the dietary and microbial influences on type 1 diabetes and draw comparisons with celiac disease.

In this Focus Review, Bar-Or and colleagues discuss the latest evidence that B cells play an important antibody-independent role in multiple sclerosis and the prospects this holds for therapeutic intervention.

Tussiwand and colleagues show that pDCs develop predominantly from IL-7R⁺ lymphoid progenitor cells and that mature pDCs are transcriptionally and functionally heterogenous, on the basis of their lymphoid or myeloid lineage.

TIGIT is a co-inhibitory receptor associated with T cell exhaustion. Tian and colleagues demonstrate that TIGIT is the predominant inhibitory receptor on NK cells in both humans and mice and that its blockade enhances NK cell–dependent rejection of tumors in experimental models.

TCR signaling initiates a signaling cascade involving the kinases Lck and Zap70 and the adaptor LAT. Weiss and colleagues discover a proline-rich motif in LAT, which facilitates interactions among Lck, LAT and Zap70 for efficient TCR signaling.

Typhoidal Salmonella is a major pathogen, but there is still a lack of knowledge about suitable vaccine antigens. Cerundolo and colleagues deep-phenotype bacteria-specific CD4⁺ T cells of Salmonella-infected volunteers to define cross-reactive and serovar-specific responses.

The cytokines IL-17A and IL-17F bind via same receptor. Iwakura and colleagues demonstrate different functions for IL-17A and IL-17F in the gut, with the latter altering the production of antimicrobial peptides with consequent effects on the microbiota, the induction of T_reg cells and immune-system homeostasis.

Liu and colleagues show that the ubiquitin E3 ligases Itch and WWP2 act together in regulating the strength of the TCR signal and differentiation toward the T_H2 lineage.

The immune response to pathogens varies substantially among humans. Netea and colleagues show that integration of multi-omics data and deep phenotyping enables prediction of cytokine production in responses to pathogens.