Targeting leukocyte migration and adhesion in Crohn’s disease and ulcerative colitis

Schlüter, Thomas; Baumgart, Daniel C.

doi:10.1007/s10787-011-0104-6

Cited by 166 publications

(113 citation statements)

References 110 publications

(108 reference statements)

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“…In addition, our data indicate that GM-CSF-activated peripheral blood monocytes from patients with CD behave the same way as GMaMs (Fig. 7) and that GM-CSF may regulate the homing molecules CCR2 and CCR6, which are involved in regulating several aspects of mucosal immunity, including the ability to mediate the recruitment of innate immune cells to the sites of epithelial inflammation (61,62).…”

Section: Discussionmentioning

confidence: 58%

Reprogramming of Monocytes by GM-CSF Contributes to Regulatory Immune Functions during Intestinal Inflammation

Däbritz

Weinhage

Varga

et al. 2015

The Journal of Immunology

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Human and murine studies showed that GM-CSF exerts beneficial effects in intestinal inflammation. To explore whether GM-CSF mediates its effects via monocytes, we analyzed effects of GM-CSF on monocytes in vitro and assessed the immunomodulatory potential of GM-CSF–activated monocytes (GMaMs) in vivo. We used microarray technology and functional assays to characterize GMaMs in vitro and used a mouse model of colitis to study GMaM functions in vivo. GM-CSF activates monocytes to increase adherence, migration, chemotaxis, and oxidative burst in vitro, and primes monocyte response to secondary microbial stimuli. In addition, GMaMs accelerate epithelial healing in vitro. Most important, in a mouse model of experimental T cell–induced colitis, GMaMs show therapeutic activity and protect mice from colitis. This is accompanied by increased production of IL-4, IL-10, and IL-13, and decreased production of IFN-γ in lamina propria mononuclear cells in vivo. Confirming this finding, GMaMs attract T cells and shape their differentiation toward Th2 by upregulating IL-4, IL-10, and IL-13 in T cells in vitro. Beneficial effects of GM-CSF in Crohn’s disease may possibly be mediated through reprogramming of monocytes to simultaneously improved bacterial clearance and induction of wound healing, as well as regulation of adaptive immunity to limit excessive inflammation.

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Section: Discussionmentioning

confidence: 58%

Reprogramming of Monocytes by GM-CSF Contributes to Regulatory Immune Functions during Intestinal Inflammation

Däbritz

Weinhage

Varga

et al. 2015

The Journal of Immunology

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“…The α subunit determines the specificity of the integrin ligand, the β subunit is connected to the cytoskeleton and affects multiple signaling pathways [Barczyk et al 2010;Thomas and Baumgart, 2012].…”

Section: Antiadhesion Molecules In Ucmentioning

confidence: 99%

The clinical potential of etrolizumab in ulcerative colitis: hypes and hopes

Fiorino

Gilardi

Danese

2016

Therap Adv Gastroenterol

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Antiadhesion molecules are effective and safe in patients with ulcerative colitis (UC). Etrolizumab, a monoclonal antibody targeting both α 4 β 7 and α E β 7 , represents a promising therapy for patients with UC, since this novel mechanism of action may be effective in blocking leukocyte recruitment both at the vascular and at the mucosal level. Preliminary studies show that etrolizumab is effective in inducing clinical response and remission, and mucosal healing. Moreover, new predictors of response have recently been identified, opening the way to a tailored therapeutic approach. This review of the literature aims to present and discuss the most recent evidence on etrolizumab in UC, focusing on the clinical implications of the use of etrolizumab in UC.

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“…The leukocyte infiltration is governed by expression of integrins; chemokine receptors (CCR) on immune cells and adhesion molecules; like intercellular adhesion molecule 1 (ICAM-1); vascular cell adhesion molecule1 (VCAM-1) and mucosal addressin cell adhesion molecule (MAdCAM-1) on the endothelium of the guts' vessels. CAM-inhibitors aim to inhibit the different subunits of these adhesion molecules [9].…”

Section: Anti-integrinsmentioning

confidence: 99%

“…In addition; although corticosteroids are able to induce clinical remission; but they are associated with lots of adverse events; and they are unable to induce mucosal healing and long term use is discouraged [7]. Azathioprine (AZA) is a potent drug to maintain clinical remission in CD; but it has a slow onset of action and long term benefit on the natural history of the disease became conflictive [8,9].…”

Section: Introductionmentioning

confidence: 99%