Volume 12 Issue 8, August 2011

NF-κB-mediated inflammatory biology can be formulated as the following five states: latency, induction, response, resolution and pathology. The first four involve carefully tuned molecular processes; pathology is the loss of control.

Twenty-five years after its identification, the transcription factor NF-κB continues to attract intense effort from a large and diverse research community. Ranjan Sen offers a personal account of the discovery of NF-κB.

Innate immune responses need to be tightly controlled to avoid autoimmune and inflammatory diseases. The atypical orphan nuclear receptor SHP has now been identified as a negative regulator of Toll-like receptor–induced activation of the transcription factor NF-κB.

The generation of Ly6C⁻ patrolling monocytes requires the transcription factor NR4A1 (Nur77). This finding provides insight into the development and function of these blood-resident cells.

Systems biology has emerged as a promising research strategy that can be applied to vaccine development. This approach can lead to the identification of new mechanisms and predictors of inactivated vaccine immunogenicity.

The protein isomerase Pin1 regulates the conformational state of signaling proteins. Lu and colleagues show that Pin1 has an essential role in Toll-like receptor signaling by regulating the adapter IRAK1.

The orphan nuclear receptor SHP is a transcriptional corepressor in the liver. Jo and colleagues show that it also acts to negatively regulate Toll-like receptor signaling at multiple levels.

Inositol phosphates are widely produced in animal and plant tissues. Luo and colleagues demonstrate that the inositol phosphate InsP7 modulates membrane translocation of the kinase Akt and downstream phosphatidylinositol-(3,4,5)-trisphosphate signaling in neutrophils.

Neutrophils migrate into tissues as innate immune responders. Nourshargh and colleagues demonstrate that neutrophils can migrate in the reverse direction in vivo under inflammatory conditions and may contribute to the dissemination of systemic inflammation.

Natural killer cells and cytotoxic T lymphocytes kill targeted cells by releasing granzymes and perforin. Lieberman and colleagues show that these lethal molecules first accumulate in endocytic vesicles, where perforin generates pores that leak granzymes into the cytosol.

Ly6C^– monocytes patrol blood vessels by crawling along uninflamed vasculature. Hedrick and colleagues show that the transcription factor NR4A1 is required for the development and survival of Ly6C^– monocytes.

Identifying molecular predictors of effective vaccination is an important clinical and technical goal. Pulendran and colleagues use a systems biology approach to study human responses to vaccination against influenza and determine the correlates of immunogenicity.

MicroRNAs are post-transcriptional regulators of gene expression. Pagani and colleagues identify specific microRNA signatures and their target genes in various human lymphoid subsets.

The transcription factor NF-κB orchestrates many facets that underlie the development and homeostasis of immune system cells and the generation of immune responses. Nature Immunologypresents six specially commissioned reviews to mark the 25th anniversary of the discovery of NF-κB.