Volume 15 Issue 11, November 2014

Neutrophils sense the size of microbial targets and respond via 'NETosis' when targets are too big to internalize and contain via phagocytosis.

Acute ablation of T cell antigen receptors (TCRs) in regulatory T cells (T_reg cells) impairs the suppressive activity of these cells, even though they retain expression of Foxp3 and CD25. TCR signaling imparts a critical role in the suppressive function of T_reg cells.

Clusters of dermal dendritic cells and T cells are required for efficient activation of T cells in skin following hapten sensitization via a process dependent on interleukin 1α (IL-1α) and the chemokine CXCL2 produced by macrophages.

Alveolar macrophages derive from fetal monocytes that seed the lungs during late embryogenesis. The cytokine GM-CSF expressed in the developing lungs induces expression of the nuclear receptor PPAR-γ, which in turn 'instructs' the differentiation of alveolar macrophage.

Mesenchymal stem cells are being considered as potential therapy for the regeneration of damaged tissues. Shi and colleagues review how these cells are influenced by inflammation and their interactions with cells of the immune system.

How neutrophils clear hyphae and other pathogens that are too large to be ingested by phagocytosis has remained unknown. Papayannopoulos et al. show that neutrophils sense microbe size and selectively release neutrophil extracellular traps in response to large pathogens.

Details of the ontogeny of alveolar macrophages remain unclear. Kopf and colleagues show that fetal monocytes give rise to alveolar macrophages in a manner dependent on the nuclear receptor PPAR-γ and the cytokine GM-CSF.

Thymocytes are positively selected upon recognition of self peptide–MHC complexes. Demetriou and colleagues show that N-glycosylation of TCR and coreceptor molecules increases the number of CD4⁺CD8⁺ thymocytes that are positively selected.

Chaperone-mediated autophagy selectively targets single cytoplasmic proteins for degradation. Macian and colleagues show that such autophagy is induced by engagement of the TCR to target negative regulators of T cell activation.

The membrane channel TRPV1 is well studied as a pain receptor, but its function beyond sensory neurons remains unclear. Raz and colleagues demonstrate that TRPV1 is also a non–store-operated calcium channel on CD4⁺ T cells with an important function in cell activation.

How APCs encounter T cells in the periphery remains unclear. Kabashima and colleagues show that dendritic cells form macrophage-dependent clusters in dermal perivascular areas for efficient in situ proliferation and activation of T cells.

Regulatory T cells help to keep adaptive immunity in check. Rudensky and colleagues show that these cells continuously require TCR signaling to maintain their cellular identity and homeostasis and to exert their suppressive ability.

Mutations in the RNA-binding protein roquin-1 are known to result in humoral autoimmunity. Heissmeyer and colleagues show that MALT1 cleavage of roquin and regnase-1 downstream of TCR signaling releases cooperatively repressed targets to promote T_H17 cell differentiation