| Title |
Targeting leukocyte migration and adhesion in Crohn’s disease and ulcerative colitis
|
|---|---|
| Published in |
Inflammopharmacology, December 2011
|
| DOI | 10.1007/s10787-011-0104-6 |
| Pubmed ID | |
| Authors |
Saskia Thomas, Daniel C. Baumgart |
| Abstract |
Crohn's disease and ulcerative colitis are two chronic inflammatory bowel diseases. Current biologic therapies are limited to blocking tumor necrosis factor alpha. However, some patients are primary non-responders, experience a loss of response, intolerance or side effects defining the urgent unmet need for novel treatments. The rapid recruitment and inappropriate retention of leukocytes is a hallmark of chronic inflammation and a potentially promising therapeutic target. We discuss the immunological mechanisms of leukocyte homing and adhesion in the gut mucosa. The interaction of lymphocytes (CD4+ T-cells, CD8+ T-cells, T(REG), T(H)1, T(H)17, B-cells), monocytes, macrophages, dendritic cells and granulocytes with endothelial and epithelial cells through integrins [α4β7 (LPAM-1), α(E)β₇ (HML1 Human Mucosal Lymphocyte Antigen 1), α₄β₁ (VLA-4), α(L)β₇, (LFA-1)] and their ligands immunoglobulin superfamily cellular adhesion molecules (CAM) (MAdCAM-1 Mucosal Addressin Cellular Adhesion Molecule 1, ICAM-1 Intercellular Cell Adhesion Molecule, VCAM-1 Vascular Cell Adhesion Molecule), fibronectin as well as chemokine receptors (CCR2, CCR4, CCR5, CCR7, CCR9, CCR10, CXCR3, CX3CR1) and chemokines [CCL5, CCL25 (TECK Thymus Expressed Chemokine), CCL28, CX3CL1, CXCL10, CXCL12] in the process of gut homing is critically reviewed and summarized in scientific cartoons. Moreover, we discuss the clinical trial results of approved and investigational antibodies and small molecules including natalizumab (anti-α₄ Tysabri®, Antegren®), AJM300 (anti-α4), etrolizumab (anti-β7, rhuMAb-Beta7), vedolizumab (anti-α4β7, LDP-02, MLN-02, MLN0002), PF-00547659 (anti-MAdCAM), Alicaforsen (anti-ICAM-1), and CCX282-B (anti-CCR9, GSK-1605786, Traficet-EN™) and their risks such as PML reported for natalizumab. Hopefully, the newer gut specific drug designs discussed in this article will have an impact on both efficacy and safety. |
Mendeley readers
The data shown below were compiled from readership statistics for 214 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 1% |
| United Kingdom | 2 | <1% |
| Netherlands | 2 | <1% |
| France | 1 | <1% |
| Unknown | 206 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 43 | 20% |
| Student > Ph. D. Student | 41 | 19% |
| Other | 26 | 12% |
| Student > Master | 26 | 12% |
| Student > Bachelor | 19 | 9% |
| Other | 37 | 17% |
| Unknown | 22 | 10% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 65 | 30% |
| Agricultural and Biological Sciences | 48 | 22% |
| Biochemistry, Genetics and Molecular Biology | 23 | 11% |
| Immunology and Microbiology | 17 | 8% |
| Pharmacology, Toxicology and Pharmaceutical Science | 9 | 4% |
| Other | 21 | 10% |
| Unknown | 31 | 14% |
Attention Score in Context
This research output has an Altmetric Attention Score of 15. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 April 2024.
All research outputs
#2,123,612
of 23,506,079 outputs
Outputs from Inflammopharmacology
#50
of 577 outputs
Outputs of similar age
#16,282
of 246,553 outputs
Outputs of similar age from Inflammopharmacology
#2
of 14 outputs
Altmetric has tracked 23,506,079 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 577 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.8. This one has done particularly well, scoring higher than 91% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 246,553 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 93% of its contemporaries.
We're also able to compare this research output to 14 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 85% of its contemporaries.