Repetitive sequences derived from transposons make up a large fraction of eukaryotic genomes and must be silenced to protect genome integrity. Repetitive elements are often found in heterochromatin; however, the roles and interactions of heterochromatin proteins in repeat regulation are poorly understood. Here we show that a diverse set of C. elegans heterochromatin proteins act together with the piRNA and nuclear RNAi pathways to silence repetitive elements and prevent genotoxic stress in the germ line. Mutants in genes encoding HPL-2/HP1, LIN-13, LIN-61, LET-418/Mi-2, and H3K9me2 histone methyltransferase MET-2/SETDB1 also show functionally redundant sterility, increased germline apoptosis, DNA repair defects, and interactions with small RNA pathways. Remarkably, fertility of heterochromatin mutants could be partially restored by inhibiting cep-1/p53, endogenous meiotic double strand breaks, or the expression of MIRAGE1 DNA transposons. Functional redundancy among factors and pathways underlies the importance of safeguarding the genome through multiple means.DOI: http://dx.doi.org/10.7554/eLife.21666.001

The suppression of inappropriate immune responses by Treg cells is one of the major ways that the body maintains immune tolerance and homeostasis. Since defects in the suppressive capacity of Treg cells underlie many different immune‐mediated diseases, there is great interest in developing ways to track the number and function of Treg cells as biomarkers of tolerance and in devising ways to enhance their function therapeutically. However, the methods of studying human Treg cells are fraught with technical challenges that can often lead to misinterpretation. The most common way to determine the suppressive capacity of human Treg cells is to measure their ability to suppress the proliferation of responding CD4+ T cells. Here, we discuss the technical considerations that must be taken into account when performing suppression of T‐cell proliferation assays with human Treg cells. We also consider how T cells may falsely appear suppressive because of dying cells in the system, improper resting of T‐cell lines prior to the assay, or insufficient proliferation of the responding T cells. We propose that, in the future, classification of a population of cells as “regulatory” should rely on more than a simple test for blockade of CD4+ T‐cell proliferation.

In 2005 a newly discovered T helper cell subset that secreted interleukin (IL)-17 became the center of attention in immunology. Initial studies painted Th17 cells as the culprit for destruction in many different autoimmune and auto-inflammatory diseases. Subsequently, the discovery of patients with primary immunodeficiencies in the IL-17 pathway taught us that Th17 cells have a critical role in defense against certain fungal and bacterial infections. Moreover, the paradoxical exacerbation of Crohn’s disease in the clinical trials of a Secukinumab (AIN457), a fully human neutralizing antibody to IL-17A, has cast into doubt a universal pro-inflammatory and harmful role for Th17 cells. Evidence now suggests that depending on the environment Th17 cells can alter their differentiation program, ultimately giving rise to either protective or pro-inflammatory cells. In this review we will summarize the evidence from patients with immunodeficiencies, autoimmune, or auto-inflammatory diseases that teaches us how the pro-inflammatory versus protective function of Th17 cells varies within the context of different human diseases.