This Research Topic entitled “History of Chemoattractant Research” collects a series of personal stories by numerous experts in the field of chemoattractant research. The individual contributions portray some key discoveries that helped to transform cell migration research into a global playing field within immunology (and beyond). Early progress had a profound effect on both academia and industry. Today, numerous academic laboratories are fully engaged in compiling a detailed road map describing the highly complex network of immune and tissue cells that respond to chemoattractants. Industrial research, on the other hand, centers on drugs that interfere with immune cell traffic in inflammatory diseases and cancer.By definition, chemoattractants include early (“classical”) chemoattractants of variable chemical composition and the large family of chemokines (chemotactic cytokines) that greatly outnumber the former compounds. As inferred from their name, all chemoattractants share the ability to induce cell migration (chemotaxis) via binding to a single class of G-protein-coupled receptors on target cells. Chemoattractant research was originally viewed as a specialty subject within cell biology. However, due to the increasing number of chemoattractants being discovered and their effect on every type of immune cells distributed throughout our body, it became quickly clear that chemoattractants constitute essential regulators of all aspects in immunity. Defects in the chemoattractant system are frequently associated with immunodeficiencies or autoimmunity/chronic diseases. We now know that the complexity of the chemokine and classical chemoattractant system perfectly mirrors the multitude of immune cells distinguished by lineage relationship, function, and tissue location. In fact, chemokine receptor profiling turned out to be highly useful for defining immune cell subsets as exemplified by the numerous T-helper subsets that we know today. Indeed, such work has led to a fundamental paradigm linking the functional specialization of distinct immune cells with their migratory behavior. No doubt, the principal and unifying function of chemoattractants is their ability to induce directional cell migration, involving processes as complex as immune cell transendothelial migration as well as chemokine gradient-controlled immune cell migration within tissues. In addition, some chemokines are able to costimulate T-cell differentiation, promote immune cell survival, or act as antimicrobial peptides in peripheral epithelial tissues. A few constitutive chemokines are essential for organ development during embryogenesis and some of these even control tumor cell relocation to secondary sites. Their importance is further emphasized by the realization that viruses have hijacked host genes encoding chemokines and their receptors in order to interfere with antiviral immunity or have evolved to use certain chemokine receptors as entry coreceptors.The following series of “short stories” provide personal accounts on key discoveries. The individual molecular discoveries enabled numerous research laboratories worldwide to unravel their significance in steady-state or pathological immune processes. Although groundbreaking in their own right, it is worth emphasizing that rapid progress in chemoattractant research was only made possible by many other laboratories whose work attached “meaning” to these early findings. The authors of this miniseries are discussing their findings in the context of time, place, and subsequent progress enabled by their discoveries. It is hoped that a wide readership will find these accounts entertaining as well as educational although those who wish to gain a more detailed knowledge are referred to the many outstanding reviews on chemokines and other chemoattractants.The field of chemokines really started in 1987 with the cloning of the human gene encoding CXCL8, which occurred in parallel in the laboratories of five independent international groups. Two stories, one by Marco Baggiolini ( 1 ) and the other by Teizo Yoshimura ( 2 ), summarize this groundbreaking discovery and give a vivid account about the friendly race that ensued from the realization that activated monocytes secreted neutrophil-specific chemoattractant activity to the molecular discovery of CXCL8. Unfortunately, and probably due to the enthusiasm shared by the research community at that time, it was decided to call CXCL8 an interleukin (IL-8), which turned out to be a misleading denomination. The three-dimensional structure of CXCL8 is a hallmark of all members of the chemokine superfamily and indicated that, in fact, chemokine-like proteins have been identified several years before CXCL8. These include IP10 (CXCL10) ( 3 ), LD78 (CCL3) ( 4 ), and TCA3 ( 5 ), the mouse ortholog of human I-309 (CCL1) ( 6 ). However, their chemoattractant activity remained obscure until well after the discovery of CXCL8. Also, platelet factor 4 (CXCL4) ( 7 – 9
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