Volume 19 Issue 4, April 2018

SWAP-70 and DEF6 prevent the cytokine IL-21–induced transcription factor IRF5 from binding to DNA and recruiting the transcription factor T-bet and thereby diminish the activation of age-associated B cells.

IL-33 is a mediator of allergic inflammation and is localized in mucosal tissues to respond rapidly to environmental insults. These include allergens themselves, which can directly activate IL-33 through their intrinsic proteolytic activity.

Systemic exposure to dietary and microbial components induces long-lasting epigenetic and metabolic changes in myeloid precursor cells, which results in enhanced proinflammatory and anti-microbial responses of mononuclear phagocytes after challenge with related or unrelated stimuli.

Autoreactive T cells exclusively recognize the roof of the binding groove of the antigen-presenting molecule CD1c after it has caved in on short headless self lipids.

The sensing of viable pathogens by the receptor TLR8 on human monocytes provides key signals that initiate the differentiation of naive CD4⁺ T cells into follicular helper T cells. Targeting TLR8 might represent a novel approach for improving immunity following vaccination.

Mosquito salivary-gland extract can modulate the host immune response. Qi and colleagues show that the salivary factor LTRIN from Aedes aegypti facilitates the transmission of Zika virus by interfering with the lymphotoxin-β receptor.

Act1 is an adaptor protein that associates with the IL-17 receptor at the cell membrane. Li and colleagues show that Act1 also exhibits unexpected RNA-binding activity and directly stabilizes select mRNAs encoding inflammatory cytokines and chemokines.

Tumor cells commonly manipulate their environment to ensure their survival. Kuan and Ziegler show that breast cancer cells release IL-1α, which acts on infiltrating myeloid cells to elicit their production of TSLP. In turn, TSLP promotes the survival of TSLPR⁺ tumor cells by upregulating expression of the pro-survival factor Bcl-2.

The cytokine IL-33 has major roles in type 2 immunity and allergy. Girard and colleagues demonstrate that a broad range of allergens across multiple kingdoms can directly cleave IL-33 via their intrinsic protease activity and convert it into a highly active processed form.

Sander and colleagues show that antigen-presenting cells detect bacterial RNA from live bacteria via TLR8 and promote T_FH cell differentiation and vaccine responses through the induction of a specific cytokine profile.

CD1 molecules present diverse lipid ligands to TCRs expressed by NKT cells. Rossjohn, Moody and colleagues show a unique form of autoreactivity with human CD1c molecules, whereby TCRs recognize a closed conformation of CD1c molecules, which are loaded with a diverse array of ‘headless’ glycolipids.

A unique subset of T-bet-expressing B cells accumulates with aging and in autoimmunity. Pernis and colleagues show that dysregulation of the transcription factor IRF5 occurs after loss of the Rho GTPase–regulatory proteins DEF6 and SWAP-70 and leads to the premature generation of age-associated B cells.