About the Cover
Innate immune response to tissue damage: (I) DAMPs released from necrotic cells and damaged tissues activate PRRs in resident, patrolling, and recruited innate immune cells, leading to the secretion of inflammatory mediators and vasodilators. (II) Activation of endothelial cells and production of CXC chemokines by innate and stromal cells recruit neutrophils. (III) Regulated activation of inflammasomes promotes regeneration of the epithelium. (IV) Migration of recruited neutrophils and inflammatory monocytes to the affected tissue. (V) Type 2 polarization and production of protumorigenic mediators. (VI) Persistent and unregulated inflammasome signaling promotes tumorigenesis. For details, see the “Masters of Immunology” article by Nowarski and colleagues on page 77 of this issue.

About the Master
Richard A. Flavell is Sterling Professor of Immunobiology at Yale School of Medicine, New Haven, Connecticut, and an Investigator of the Howard Hughes Medical Institute, Home Institution. He received his B.Sc. (Honors) and Ph.D. in biochemistry from the University of Hull, England, and performed postdoctoral work with Piet Borst in Amsterdam and Charles Weissmann in Zurich. Before joining Yale, Flavell was Assistant Professor at the University of Amsterdam; Head of the Laboratory of Gene Structure and Expression at the National Institute for Medical Research, Mill Hill, London; and President and Chief Scientific Officer of Biogen Research Corporation, Cambridge, Massachusetts. Dr. Flavell is a fellow of the British Royal Society and a member of both the US National Academy of Sciences and the Institute of Medicine.
Richard Flavell is co-discoverer of introns in cellular genes; he showed DNA methylation correlates inversely with, and prevents, gene expression. He was the first to develop reverse genetics, with Weissmann, and pioneered the approach in vivo to study function. The Flavell laboratory uses mouse genetics to study activation in immunity and autoimmunity, apoptosis, and T-cell tolerance. Flavell was instrumental in discovering the molecular basis of T-cell differentiation from precursor cells into differentiated subsets, which led to the discovery of GATA3 as a critical regulator of the Th2 response and the first example of such a molecule in Th cell differentiation. He demonstrated the first case of regulation of gene expression in trans, via “chromosome kissing.” The Flavell laboratory has elucidated the role of TGF-β in the regulation of immune response, which has relevance both to the control of autoimmune diseases and to the evasion of immune response by tumors.
The Flavell laboratory has discovered the role of several Toll-like receptors and intracellular Nod-like receptor families in innate immune response, which led to the elucidation of function of Nod2 in inflammatory bowel diseases (IBD) and Nlrp proteins in the production of IL-1. Most recently, he has established a connection between inflammasomes, microbial homeostasis, and chronic diseases. He showed that inflammasome dysfunction causes dysbiosis of the microbiota, which, in conjunction with a susceptible diet, leads to IBD and various metabolic syndromes.