Enhanced Recruitment of CX3CR1+ T Cells by Mucosal Endothelial Cell–Derived Fractalkine in Inflammatory Bowel Disease

Sans, Miquel; Danese, Silvio; Motte, Carol A. de la; Souza, Heitor Siffert Pereira de; Rivera-Reyes, Brenda M.; West, Gail; Phillips, Murray G.; Katz, Jeffry; Fiocchi, Claudio

doi:10.1053/j.gastro.2006.10.010

Cited by 68 publications

(52 citation statements)

References 67 publications

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“…IFN-g alone did not augment the production of IL-6, IL-8, or sFKN. However, combining TNF-a and IFN-g had a clear synergistic effect on sFKN production by renal and lung MECs, as previously reported in HUVECs and intestinal MECs (27).…”

Section: Production Of Inflammatory Cytokines and Chemokines By Tissusupporting

confidence: 83%

Tissue-Specific Microvascular Endothelial Cells Show Distinct Capacity To Activate NK Cells: Implications for the Pathophysiology of Granulomatosis with Polyangiitis

Tognarelli

Gayet

Lambert

et al. 2014

The Journal of Immunology

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The relevance of tissue specificity of microvascular endothelial cells (MECs) in the response to inflammatory stimuli and sensitivity to immune cell–mediated injury is not well defined. We hypothesized that such MEC characteristics might shape their interaction with NK cells through the use of different adhesion molecules and NK cell receptor ligands or the release of different soluble factors and render them more or less vulnerable to NK cell injury during autoimmune vasculitis, such as granulomatosis with polyangiitis (GPA). To generate a comprehensive expression profile of human MECs of renal, lung, and dermal tissue origin, we characterized, in detail, their response to inflammatory cytokines and to proteinase 3, a major autoantigen in GPA, and analyzed the effects on NK cell activation. In this study, we show that renal MECs were more susceptible than lung and dermal MECs to the effect of inflammatory signals, showing upregulation of ICAM-1 and VCAM-1 on their surface, as well as release of CCL2, soluble fractalkine, and soluble VCAM-1. Proteinase 3–stimulated renal and lung MECs triggered CD107a degranulation in control NK cell. Notably, NK cells from GPA patients expressed markers of recent in vivo activation (CD69, CD107a), degranulated more efficiently than did control NK cells in the presence of renal MECs, and induced direct killing of renal MECs in vitro. These results suggest that, upon inflammatory conditions in GPA, renal MECs may contribute to the recruitment and activation of NK cells in the target vessel wall, which may participate in the necrotizing vasculitis of the kidney during this disease.

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Section: Production Of Inflammatory Cytokines and Chemokines By Tissusupporting

confidence: 83%

Tissue-Specific Microvascular Endothelial Cells Show Distinct Capacity To Activate NK Cells: Implications for the Pathophysiology of Granulomatosis with Polyangiitis

Tognarelli

Gayet

Lambert

et al. 2014

The Journal of Immunology

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“…Moreover, greater numbers of T cells expressing CX 3 CR1 are found in the circulation of IBD patients than in healthy subjects. 23 These observations indicate FKN as an important mediator of endothelium-leukocyte interaction in intestinal inflammation, suggesting a role for EC-derived FKN in the induction of a localized proinflammatory response through multiple complementary functions that include leukocyte retention, integrin affinity up-regulation, chemoattraction, and transmigration.…”

Section: Microvascular Endothelium and Leukocyte Recruitment In Ibdmentioning

confidence: 87%

Multiple Pathogenic Roles of Microvasculature in Inflammatory Bowel Disease: A Jack of All Trades

Deban

Correale

Vetrano

et al. 2008

The American Journal of Pathology

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125

100

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The etiology of Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel disease (IBD), is still largely unknown. However, it is now clear that the abnormalities underlying pathogenesis of intestinal inflammation are not restricted to those mediated by classic immune cells but also involve nonimmune cells. In particular, advances in vascular biology have outlined a central and multifaceted pathogenic role for the microcirculation in the initiation and perpetuation of IBD. The microcirculation and its endothelial lining play a crucial role in mucosal immune homeostasis through tight regulation of the nature and magnitude of leukocyte migration from the intravascular to the interstitial space. Chronically inflamed IBD microvessels display significant alterations in microvascular physiology and function compared with vessels from healthy and uninvolved IBD intestine. The investigation into human IBD has demonstrated how endothelial activation present in chronically inflamed IBD microvessels results in a functional phenotype that also includes leakiness, chemokine and cytokine expression, procoagulant activity, and angiogenesis. This review contemplates the newly uncovered contribution of intestinal microcirculation to pathogenesis and maintenance of chronic intestinal inflammation. In particular, we assess the multiple roles of the microvascular endothelium in innate immunity, leukocyte recruitment, coagulation and perfusion, and immune-driven angiogenesis in IBD.

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“…+ binds fractalkine/CX 3 CL1, which is expressed (in a soluble and a membrane-bound form) by intestinal epithelial and endothelial cells (14,15). In the particular case of the intestine, DCs play a central role in sampling and processing luminal Ags (16).…”

mentioning

confidence: 99%

Enteric Flora Expands Gut Lamina Propria CX3CR1+ Dendritic Cells Supporting Inflammatory Immune Responses under Normal and Inflammatory Conditions

Niess

Adler

2010

The Journal of Immunology

183

154

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CD103 or CX3CR1 surface expression defines distinct dendritic cells (DCs) and macrophages in the murine lamina propria of the colon (cLP). We investigated the surface marker and functional phenotype of CD103+ and CX3CR1+ cLP DCs and their role in transfer colitis. cLP CD11c+ cells were isolated from specific pathogen-free or germ-free mice to elucidate the role of the commensal flora in their development. The cLP CD11c+ cells are a heterogeneous cell population that includes 16% CX3CR1+, 34% CD103+, 30% CD103−CX3CR1− DCs, and 17% CD68+/F4/80+CX3CR1+CD11c+ macrophages. All DCs expressed high levels of MHC II but low levels of costimulatory (CD40, CD86, and CD80) and coinhibitory (programmed death ligand-1) molecules. Ex vivo confocal microscopy demonstrated that CX3CR1+CD11c+ cells, but not CD103+ DCs, were reduced in the cLP of germ-free (CX3CR1-GFP) mice. The absence of the enteric flora prevents the formation of transepithelial processes by the CX3CR1+ DCs. CX3CR1+ DCs preferentially supported Th1/Th17 CD4 T cell differentiation. CD103+ DCs preferentially induced the differentiation of Foxp3-expressing regulatory T cells. The stimulation of cLP DCs with fractalkine/CX3CL1 increased the release of IL-6 and TNF-α. In the absence of CX3CR1, the CD45RBhigh CD4 transfer colitis was suppressed and associated with reduced numbers of DCs in the mesenteric lymph nodes and a reduction in serum IFN-γ and IL-17. The local bacteria-driven accumulation of CX3CR1+ DCs seems to support inflammatory immune responses.

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Enhanced Recruitment of CX3CR1+ T Cells by Mucosal Endothelial Cell–Derived Fractalkine in Inflammatory Bowel Disease

Cited by 68 publications

References 67 publications

Tissue-Specific Microvascular Endothelial Cells Show Distinct Capacity To Activate NK Cells: Implications for the Pathophysiology of Granulomatosis with Polyangiitis

Tissue-Specific Microvascular Endothelial Cells Show Distinct Capacity To Activate NK Cells: Implications for the Pathophysiology of Granulomatosis with Polyangiitis

Multiple Pathogenic Roles of Microvasculature in Inflammatory Bowel Disease: A Jack of All Trades

Enteric Flora Expands Gut Lamina Propria CX3CR1+ Dendritic Cells Supporting Inflammatory Immune Responses under Normal and Inflammatory Conditions

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