Volume 14 Issue 5, May 2013

Interleukin 17 (IL-17) confers protection against Trypanosoma cruzi. Surprisingly, B cells are the relevant source, producing IL-17 via a unique pathway independent of the transcription factor RORγt, induced by T. cruzi trans-sialidase.

Obesity induces metabolic stress and is associated with inflammation. A cellular pathway now links SIRT2, a deacetylase involved in metabolic processes, to cytoskeleton remodelling and activation of the NLRP3 inflammasome.

T cell activation requires an influx of amino acids. Slc7a5, an amino-acid transporter induced by the T cell antigen receptor, facilitates the influx of large neutral amino acids and in doing so promotes metabolic reprogramming necessary for T cell differentiation.

The newly identified steroid ligand of the receptor EBI2 (GPCR183), 7α,25-dihydroxycholesterol, is required for the positioning of splenic CD4⁺ dendritic cells in bridging channels to prime T cells for an efficient antibody response.

How hematopoietic stem cells coordinate self-renewal and differentiation remains unclear. Steidl and colleagues show that the transcription factor and chromatin remodeler Satb1 is required for their self-renewal.

Precise lymphoid tissue architecture is needed to generate adaptive immune responses. Brink and colleagues show that CD4⁺ DCs express the chemotactic receptor EBI2, which is required for their splenic positioning and capture of particulate blood-borne antigens.

Much is known about the activation of the NLRP3 inflammasome; however, the control of its physical assembly is less well understood. Akira and colleagues demonstrate that acetylated tubulin drives assembly of the inflammasome at mitochondria.

Unchecked inflammation can lead to tissue damage. Liu and colleagues show that the transcription factor Miz1 recruits the histone deacetylase HDAC1 to restore repression of Cebpd transcription, which is necessary for the termination of LPS-induced inflammatory responses.

Inflammation needs to be tightly regulated to avoid immunopathology. Mallampalli and colleagues show that a system of F box proteins tunes proinflammatory signaling by degrading TRAF adaptor proteins.

Autophagocytic disposal of mitochondria (mitophagy) is important for regulating inflammation. Kanneganti and colleagues show that RIP2 kinase–initiated mitophagy is critical for dampening virally triggered immunopathology.

T cell division is an intense metabolic process, and meeting its demands requires extensive metabolic reprogramming of the cell. Bensinger and colleagues demonstrate that SREBPs are critical for this reprogramming.

T cell activation triggers proliferation and effector-cell differentiation. Cantrell and colleagues show that TCR signaling induces upregulation of amino-acid transporters necessary for metabolic reprogramming via the kinase complex mTORC1 and transcription factor c-Myc.

Tissue-resident effector memory T cells respond rapidly after reencountering antigen. Masopust and colleagues show that memory CD8⁺ T cells also induce the release of chemokines, then recruit more memory cells to the site of infection.

Antibody production is the main effector function of B cells. Rawlings and colleagues show that Trypanosome cruzi induces rapid IL-17 production by B cells that is required for parasite control.