However, given the multicellular immune cell infiltrate in IBD, the role of several chemokine receptors in the complex chemokine network in the inflamed mucosa remains incompletely defined. Both experimental work in mouse models and evidence from clinical studies support an important role for several chemokine receptors in the pathogenesis of IBD ( 8). Besides their manifest capacity to coordinate immune cell migration and positioning, various other regulatory roles during growth, survival, or cytokine production of immune cells have been revealed recently ( 7). Although nearly any cell type can produce chemokines upon stimulation, immune cells have been demonstrated to be a major source during inflammatory reactions. Through binding to their cognate receptors, which belong to the class A rhodopsin-like family of G-proteinвЂ“coupled receptors, they play fundamental roles in normal physiology as well as in inflammatory and infectious diseases ( 6). Yet, the complex immunological processes that are important for the fine-tuning of cytokine signals during intestinal immune responses are incompletely understood.Д¬hemokines comprise a group of small cytokines with the capacity to induce directional leukocyte migration. Consistently, the modulation of cytokine responses can have deleterious or therapeutic effects and such therapeutic strategies are of increasing clinical importance ( 5). While immune cell derived cytokine production is indispensable for mucosal homeostasis and can robustly protect the mucosa from pathogen entry, dysregulated cytokine responses have a crucial role in the pathogenesis of IBD by controlling several aspects of the inflammatory reaction ( 4). However, in lesions of patients with IBD, the aberrant inflammatory process is accompanied by a very prominent infiltrate of immune cells of both the innate and adaptive immune system. Although the etiology of IBD still remains incompletely understood, it is generally agreed that a complex interplay between genetic, environmental, and immunological factors contributes to disease initiation and progression ( 2, 3).Д®ven in the steady state, the intestinal mucosa is populated by a diverse spectrum of immune cells reflecting its continuous stimulation by luminal antigens. While both diseases are chronic and relapsing inflammatory diseases, they can typically be distinguished by the location of inflammatory lesions in the gastrointestinal tract and by the pattern of histological alterations in the bowel wall.

CrohnвЂ™s disease (CD) and ulcerative colitis (UC) are the two main manifestations of IBD ( 1). Inflammatory bowel diseases (IBD) are idiopathic inflammatory disorders of the gastrointestinal tract. Modulation of this regulatory circuit may represent a new strategy to treat inflammatory bowel disease in humans. Our data therefore suggest that this pathway supports tissue-specific ILC functions important for intestinal homeostasis. Moreover, we newly identified CCR8 expression on a subgroup of intestinal innate lymphoid cells producing IFN-Оі and linked a functional CCL1/CCR8 axis with their abundance in the gut. Further experiments revealed that this gut protective function of CCR8 seems to be selectively mediated by the chemotactic ligand CCL1, which was particularly produced by intestinal macrophages during colitis. We found that CCR8 в€’/в€’ mice compared to wildtype controls developed strong weight loss accompanied by increased histological and endoscopic signs of mucosal damage. In order to further characterize this complex immune cell network in intestinal inflammation, we investigated the contribution of the chemokine receptor CCR8 to development of colitis using a mouse model of experimental inflammation. These mediators perpetuate intestinal inflammation or may contribute to mucosal protection depending on the cellular context. In lesions of patients with inflammatory bowel disease, an aberrant inflammatory process is characterized by a very prominent infiltrate of activated immune cells producing cytokines and chemokines.

2Medical Immunology Campus Erlangen, FAU Erlangen-NГјrnberg, Erlangen, GermanyДЄ diverse spectrum of immune cells populates the intestinal mucosa reflecting the continuous stimulation by luminal antigens.

1Medizinische Klinik 1, UniversitГ¤tsklinikum Erlangen, Friedrich-Alexander-UniversitГ¤t Erlangen-NГјrnberg, Erlangen, Germany.Neurath 1,2, Christoph Becker 1,2 and Stefan Wirtz 1,2* Le Kang 1, Angelika Schmalzl 1, Tamara Leupold 1, Miguel Gonzalez-Acera 1, Raja Atreya 1, Markus F.

Ccr 8