http://immunol.nature.com • february 2001 • volume 2 no 2 • nature immunology

They permeate every nook and cranny: immunology isnow replete with chemokines, those cytokines thatcause the directed migration of leukocytes. Immuno-logists were almost caught unawares. Years ago, onlythose interested in inflammation seemed concernedwith the travelings of leukocytes and the molecules thatdirected their journeys. But the realization that a majorcoreceptor for HIV was a chemokine receptor catapult-ed the study of chemokines into the mainstream.Suddenly those who had been analyzing chemokines allalong seemed prescient.

And chemokines have continued to surprise us. Theirnumbers keep mounting, with more than 40 identifiedso far, many of which share specificity for the numerousreceptors. Together, the chemokine network seems tosupply the needed subtlety and necessary nuance in theeffort to stave off infections and infiltrations. Althoughtheir primary roles can be thought of as traffic coordi-nators for an organism’s defense system, they are alsoresponsible for orchestrating and carefully balancingjust when and which cell or protein chimes in.

In this issue of Nature Immunology we celebrate thecontributions that these proteins, and those who haveinvestigated them, have made to our understanding ofthe development of both the immune system andimmune responses. Half of the journal this month isdevoted to chemokines, from Reviews and Correspon-dence to a collection of Round-ups that summarize themost interesting recent papers on chemokines in otherjournals.

Our special online Focus on Chemokines(http://immunol.nature.com/special_focus/chemokine)is free to all who register. With the generous help of ouradvisors in the scientific community (we are mostindebted to the authors of our Review articles and to M.Baggiolini and A. Lanzavecchia), we have compiled andpresent on the site an annotated list of important papersthat we consider “selected classics”. To further aid thosecurious about “all things chemokine”, one can also findon our site a compilation of links for free access to themajor papers on chemokines published in Nature andthe other monthly publications of the Nature PublishingGroup, such as Nature Medicine or NatureBiotechnology. Our Chemokine Focus website will beavailable free-of-charge for 3 months, during whichtime we will update the Round-ups on a monthly basis.After 1 May 2001, however, the site will be available toour subscribers only.

For the reader who needs to get his or her bearings,be sure to look at Mackay’s overview of the multifac-eted roles of chemokines in the normal regulation and

movement of immune system cells and their involve-ment in its dysregulation. Focusing on lymphocytes intheir review, Moser and Loetscher delve into howchemokines affect lymphopoiesis and recirculation andtheir role in moving lymphocytes to the site of an infec-tion or inflammation.

Chemokines and cytokines do more than just tellwhite blood cells where to go. Luther and Cysterdescribe how chemokines can also affect the differenti-ation of T cells by influencing the quality and the quan-tity of their responses. The presence or absence of cer-tain chemokines can determine whether helper T cellsbecome polarized as type 1 or type 2 responders. Thechemokines’ ability to influence cytokine productionand a T cell’s response to various other environmentalstimuli begs the next question. How do the chemokinereceptors transmit such complex signals? Thelenreviews the trimeric G protein–linked and other signal-ing pathways that emanate from chemokine binding.Although our understanding of these processes is in itsinfancy, the field seems on the brink of major break-throughs in “receptor cross-talk” and unraveling theintertwined threads that initiate and carry throughdirected movement.

With the myriad of chemokines and receptors, howcan one hope to harness this system to manipulateimmunity? Redundancies, backup factors and safetynets abound. One way to find therapeutic direction isto take our cues from viruses. As discussed in a reviewby Murphy, some virus families—such as herpesvirus,poxvirus and retroviruses—have already determinedthe most useful chemokines and receptors to thwart,subvert or mimic. Thus out of the multitude, a few keycomponents can be exploited to further a differentprogram.

These clues may be helpful in the search forchemokine agonists or antagonists that may aid in thetreatment of multiple human disease conditions. Intheir review, Gerard and Rollins discuss a number ofconditions in which the expression of chemokines isaltered or chemokine receptors are inappropriatelyexpressed. Multiple sclerosis, HIV/AIDS, arthritis,cancer and heart disease are just some of the patholog-ical settings in which chemokines could potentiallyyield treatments.

We hope to provide for you a snapshot of howchemokine research is presently impacting immunolo-gy. These are exciting times, with much to be learnedand new opportunities to move basic research to theclinic. Enjoy the issue and our Chemokine Focus web-site—and let us know what you think.

EDITORIAL

Celebrating chemokines

volume 2 no 2 february 2001

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