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Paneth cell dysfunction has been linked to Crohn's disease. Nod2 and LRRK2, two genetic susceptibility factors for this disease, are now shown to have a role in regulating the sorting of lysozyme in Paneth cells and its secretion into the crypt space and, ultimately, in maintenance of the intestinal barrier.
Follicular helper T cells (TFH cells) differentiate from naive T cells, but the picture of this differentiation process remains incomplete. Two studies now identify the related transcriptional regulators TCF-1 and LEF-1 as important early participants in this process.
A previously unknown function for TH17 cell–derived IL-26 as a direct antimicrobial agent and activator of DNA-sensing innate immunity is now reported.
Intrathymic expression of self antigens is key for central tolerance. RNA-sequencing analysis of tissue-restricted antigens in individual medullary thymic epithelial cells reveals co-ordination in the gene-expression patterns that ensures effective self-representation for the production of self-tolerant T cells.
Billions of cells in the body die through apoptosis every day and are cleared by both professional and non-professional phagocytes. Arandjelovic and Ravichandran review how apoptotic cell clearance is critical for immune homeostasis.
Targeted deletion of the transcription factor XBP1 in hematopoietic stem cells selectively prevents eosinophil maturation in the bone marrow without affecting other lineages of the immune system.
Fat-associated lymphoid clusters (FALCs) are non-classical secondary lymphoid organs of the body cavities. The formation and maturation of FALCs are driven by tumor-necrosis factor and are further enhanced by invariant natural killer T cells.
As the cytosolic guardian for many microbial and sterile inflammatory insults, NLRP3 is best appreciated for its innate immunological role mediating inflammasome activation. Now NLRP3 debuts as a transcription factor key for TH2 polarization.
Effective anti-tumor immune therapy in solid tumors relies on the presence of effector T cells. Inhibition of the dipeptidylpeptidase DPP4 (CD26) enhances chemokine CXCL10–mediated infiltration of lymphocytes into the tumor parenchyma, which results in diminished tumor growth.
Type I and III interferons share similar antiviral properties, but there are some important distinctions. Hartmann and colleagues review the specialized functions of type III interferons, including their ability to mediate antiviral functions at barrier surfaces.
Deep-sequencing analyses of immunoglobulin variable-segment genes from antibody-secreting cells have allowed comparisons of conventional immunization responses to disease flares experienced by patients with systemic lupus erythematosus. Such analyses provide insight into B cell recruitment and differentiation processes yielding expanded clones that contribute to this complex autoimmune disease.
Sirtuin-1 (Sirt1), a protein deacetylase known for its multiple cellular functions, including roles in metabolism, stress response and aging, is a post-translational modulator of autoimmune regulator (Aire) in central immunotolerance.
Dendritic cell progenitors commit to a specific conventional dendritic cell fate earlier than previously thought, by initiating transcription-factor regulatory circuits unique to their subtype.
Researchers gathered at the Wellcome Trust Genome Campus in Hinxton, Cambridge, for the first Innate Immune Memory Conference dedicated to the adaptive characteristics of innate immunity, to further the understanding of this newly described immunological process that probably has a central role in host defense and inflammation.
Gerlic and colleagues examine the role of cell death, particularly necroptosis, in inflammation, in the context of recent insights into the roles of the key necroptosis effector molecules RIPK1, RIPK3 and MLKL.
Like T cells and B cells, innate lymphoid cells (ILCs) develop from common lymphoid progenitors, but how commitment to the ILC lineage is regulated has remained unclear. The transcriptional regulator TOX is important in this process.
The anti-inflammatory molecule A20 inhibits necroptotic cell death by inhibiting ubiquitination of the kinase RIPK3 at the Lys5 residue and preventing excessive formation of the RIPK1-RIPK3 necroptotic complex.
Due to their role in regulating DNA-methylation patterns, the TET proteins, in particular TET2, have emerged as key participants in tumorigenesis. Now the spotlight shifts to TET1 and its role as a tumor suppressor in lymphomagenesis.
An effect of host genetic variation on susceptibility to HIV-1 was identified early in the pandemic. McLaren and Carrington discuss the extent to which additional polymorphisms influence HIV-1 disease progression and how analysis of data sets may discover novel gene variants that affect the outcome of HIV-1.