Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
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.
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.
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.
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.
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.
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.
The clearance of apoptotic cells requires recognition by members of the TAM receptor tyrosine kinase family. Lemke and colleagues show that the TAM receptors Mer and Axl have distinct functions in tolerance induction and proinflammatory responses, respectively.
Cellular metabolism seems to dictate immune responses. Weinmann and colleagues show that the transcription factor Bcl-6 opposes the action of c-Myc and Hif-1α to suppress expression of genes encoding key glycolytic enzymes and transporters.
High endothelial vessels (HEVs) provide the conduit for blood-borne leukocytes to enter lymph nodes. Butcher and colleagues report transcriptional profiles of various endothelial cell populations that can explain functional differences of homing-molecule modifications.
The role of neutrophils in helminth infection has been relatively unclear. Gause and colleagues demonstrate that neutrophils are involved in the priming of an M2 macrophage response that mediates long-term protection against helminth infection.
Naive B and T cells exist in discrete zones in lymph nodes. Turley and colleagues demonstrate that a distinct subset of fibroblastic reticular cells reside in B cell zones, where they sustain B cell survival by providing BAFF.
Many tissue-resident macrophages are derived from embryonic precursors. Mowat and colleagues show that embryonic precursor cells seed gut tissues but at weaning transition to a bone marrow–derived macrophage population that requires continual replenishment.
Senescent T cells have increased activity of the mitogen-activated protein kinase p38. Akbar and colleagues show that such cells lack the canonical and alternative p38-activation pathways and instead induce kinase AMPK–dependent autophosphorylation of p38.
The transcription factor ThPOK promotes CD4+ T cell differentiation in the thymus. Bosselut and colleagues show that ThPOK maintains CD4+ T lineage integrity and is required for proper TH1 and TH2 differentiation.
The phosphatase PTPN22 is associated with human autoimmune disease. Zamoyska and colleagues demonstrate that loss of PTPN22 enhances T cell responses to weak agonists and unmasks self-reactivity.
The sensors of damage and danger in the nematode epidermis are unclear. Ewbank and colleagues show that the G protein–coupled receptor DCAR-1 detects epithelial damage elicited mechanically or by a fungal pathogen.
Alternatively activated (M2) macrophages use fatty acid oxidation for their metabolic needs. Pearce and colleagues show that triacylglycerols metabolized by lysosomal acid lipase are required for the M2 activation of and function of macrophages.
The factors that drive the differentiation of human follicular helper cells remain largely undefined. Ueno and colleagues show that TGF-β complements STAT3- and STAT4-activating cytokines to promote the initial differentiation of such cells.
RIG-I-like receptors are activated by viral and other foreign RNAs. Stetson and colleagues show that the RNA exosome enzyme SKIV2L prevents RIG-I activation by endogenous RNAs generated by IRE-1 in stressed cells.