scholarly journals Targeting Immune Cell Trafficking – Insights From Research Models and Implications for Future IBD Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Maximilian Wiendl ◽  
Emily Becker ◽  
Tanja M. Müller ◽  
Caroline J. Voskens ◽  
Markus F. Neurath ◽  
...  
Keyword(s):  
Immune Cell ◽  
Therapeutic Interventions ◽  
Cell Trafficking ◽  
Future Directions ◽  
Immune Cell Trafficking ◽  
Multifactorial Diseases ◽  
Medical Need ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC) are multifactorial diseases with still unknown aetiology and an increasing prevalence and incidence worldwide. Despite plentiful therapeutic options for IBDs, the lack or loss of response in certain patients demands the development of further treatments to tackle this unmet medical need. In recent years, the success of the anti-α4β7 antibody vedolizumab highlighted the potential of targeting the homing of immune cells, which is now an important pillar of IBD therapy. Due to its complexity, leukocyte trafficking and the involved molecules offer a largely untapped resource for a plethora of potential therapeutic interventions. In this review, we aim to summarise current and future directions of specifically interfering with immune cell trafficking. We will comment on concepts of homing, retention and recirculation and particularly focus on the role of tissue-derived chemokines. Moreover, we will give an overview of the mode of action of drugs currently in use or still in the pipeline, highlighting their mechanisms and potential to reduce disease burden.

Immune cell trafficking and retention in inflammatory bowel disease: mechanistic insights and therapeutic advances

Gut ◽  
2019 ◽  
Vol 68 (9) ◽  
pp. 1688-1700 ◽  
Author(s):  
Sebastian Zundler ◽  
Emily Becker ◽  
Lisa Lou Schulze ◽  
Markus F Neurath
Keyword(s):  
Immune Cell ◽  
Cell Trafficking ◽  
T Cell Trafficking ◽  
Immune Cell Trafficking ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Immune Cell Subpopulations ◽  
Cell Subpopulations ◽  
G Protein Coupled ◽  
Lymphocyte Populations

Intestinal immune cell trafficking has been identified as a central event in the pathogenesis of inflammatory bowel diseases (IBD). Intensive research on different aspects of the immune mechanisms controlling and controlled by T cell trafficking and retention has led to the approval of the anti-α4β7 antibody vedolizumab, the ongoing development of a number of further anti-trafficking agents (ATAs) such as the anti-β7 antibody etrolizumab or the anti-MAdCAM-1 antibody ontamalimab and the identification of potential future targets like G-protein coupled receptor 15. However, several aspects of the biology of immune cell trafficking and regarding the mechanism of action of ATAs are still unclear, for example, which impact these compounds have on the trafficking of non-lymphocyte populations like monocytes and how precisely these therapies differ with regard to their effect on immune cell subpopulations. This review will summarise recent advances of basic science in the field of intestinal immune cell trafficking and discuss these findings with regard to different pharmacological approaches from a translational perspective.

scholarly journals Immunotherapy in CNS cancers: the role of immune cell trafficking

2018 ◽  
Vol 21 (1) ◽  
pp. 37-46 ◽  
Author(s):  
Nivedita M Ratnam ◽  
Mark R Gilbert ◽  
Amber J Giles
Keyword(s):  
Immune Cell ◽  
Cell Trafficking ◽  
Immune Cell Trafficking

scholarly journals Vitamin D Modulates Intestinal Microbiota in Inflammatory Bowel Diseases

2020 ◽  
Author(s):  
Carolina Battistini ◽  
Rafael Ballan ◽  
Marcos Herkenhoff ◽  
Susana Saad ◽  
Jun Sun
Keyword(s):  
Vitamin D ◽  
Gut Microbiota ◽  
Disease Activity ◽  
Chronic Inflammation ◽  
Immune Cell ◽  
Future Directions ◽  
Dihydroxyvitamin D3 ◽  
Host Interactions ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal0 tract (GIT), including Crohn’s disease (CD) and ulcerative colitis (UC), which differ in the location and lesion extensions. Both diseases are associated with microbiota dysbiosis, with a reduced population of butyrate-producing species, abnormal inflammatory response, and micronutrient deficiency (e. g. vitamin D hypovitaminosis). Vitamin D (VitD) is involved in immune cell differentiation, gut microbiota modulation, gene transcription, and barrier integrity. Vitamin D receptor (VDR) regulates the biological actions of the active VitD (1α, 25-dihydroxyvitamin D3), and is involved in the genetic, environmental, immune, and microbial aspects of IBD. VitD deficiency is correlated with disease activity and its administration targeting a concentration of 30 ng/mL may have the potential to reduce disease activity. Moreover, VDR regulates functions of T cells and Paneth cells and modulates release of antimicrobial peptides in gut microbiota-host interactions. Meanwhile, beneficial microbial metabolites, e.g. butyrate, upregulate the VDR signaling. In this review, we summarize the clinical progress and mechanism studies on VitD /VDR related to gut microbiota modulation in IBD. We also discuss epigenetics in IBD and the probiotic regulation of VDR. Furthermore, we discuss the existing challenges and future directions. There is a lack of well-designed clinical trials exploring the appropriate dose and the influence of gender, age, ethnicity, genetics, microbiome, and metabolic disorders in IBD subtypes. To move forward, we need well-designed therapeutic studies to examine whether enhanced vitamin D will restore functions of VDR and microbiome in inhibiting chronic inflammation.

Role of the lymphatic vasculature in cardiovascular medicine

Heart ◽  
2019 ◽  
Vol 105 (23) ◽  
pp. 1777-1784 ◽  
Author(s):  
Niklas Telinius ◽  
Vibeke Elisabeth Hjortdal
Keyword(s):  
Immune Cell ◽  
Treatment Options ◽  
Molecular Medicine ◽  
Future Research ◽  
Cell Trafficking ◽  
Cardiovascular Medicine ◽  
Immune Cell Trafficking ◽  
Lymphatic Vasculature ◽  
Factor C

The lymphatic vasculature has traditionally been considered important for removal of excessive fluid from the interstitial space, absorption of fat from the intestine and the immune system. Advances in molecular medicine and imaging have provided us with new tools to study the lymphatics. This has revealed that the vessels are actively involved in regulation of immune cell trafficking and inflammation. We now know much about how new lymphatic vessels are created (lymphangiogenesis) and that this is important in, for example, wound healing and tissue repair. The best characterised pathway for lymphangiogenesis is the vascular endothelial growth factor C (VEGF-C)/VEGFR3 pathway. Over recent years, there has been an increasing interest in the role of the lymphatics in cardiovascular medicine. Preclinical studies have shown that lymphangiogenesis and immune cell trafficking play a role in cardiovascular conditions such as atherosclerosis, recovery after myocardial infarction and rejection of cardiac allografts. Targeting the VEGF-C/VEGFR3 pathway can be beneficial in these conditions. The clinical spectrum of lymphatic abnormalities and lymphoedema is wide and overlaps with congenital heart disease. Important long-term complications to the Fontan circulation involves the lymphatics. New and improved imaging modalities has improved our understanding and management of these patients. Lymphatic leaks and flow abnormalities can be successfully treated, minimally invasively, with percutaneous embolisation. Future research will prove if the preclinical findings that point to a role of the lymphatics in several cardiovascular conditions will result in new treatment options.

The Role of Lysophospholipids in Immune Cell Trafficking and Inflammation

2016 ◽  
pp. 459-471
Author(s):  
Masayuki Miyasaka ◽  
Akira Takeda ◽  
Erina Hata ◽  
Naoko Sasaki ◽  
Eiji Umemoto ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Trafficking ◽  
Immune Cell Trafficking

scholarly journals Vitamin D Modulates Intestinal Microbiota in Inflammatory Bowel Diseases

2020 ◽  
Vol 22 (1) ◽  
pp. 362
Author(s):  
Carolina Battistini ◽  
Rafael Ballan ◽  
Marcos Edgar Herkenhoff ◽  
Susana Marta Isay Saad ◽  
Jun Sun
Keyword(s):  
Vitamin D ◽  
Gut Microbiota ◽  
Disease Activity ◽  
Chronic Inflammation ◽  
Immune Cell ◽  
Future Directions ◽  
Dihydroxyvitamin D3 ◽  
Host Interactions ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract (GIT), including Crohn’s disease (CD) and ulcerative colitis (UC), which differ in the location and lesion extensions. Both diseases are associated with microbiota dysbiosis, with a reduced population of butyrate-producing species, abnormal inflammatory response, and micronutrient deficiency (e.g., vitamin D hypovitaminosis). Vitamin D (VitD) is involved in immune cell differentiation, gut microbiota modulation, gene transcription, and barrier integrity. Vitamin D receptor (VDR) regulates the biological actions of the active VitD (1α,25-dihydroxyvitamin D3), and is involved in the genetic, environmental, immune, and microbial aspects of IBD. VitD deficiency is correlated with disease activity and its administration targeting a concentration of 30 ng/mL may have the potential to reduce disease activity. Moreover, VDR regulates functions of T cells and Paneth cells and modulates release of antimicrobial peptides in gut microbiota-host interactions. Meanwhile, beneficial microbial metabolites, e.g., butyrate, upregulate the VDR signaling. In this review, we summarize the clinical progress and mechanism studies on VitD/VDR related to gut microbiota modulation in IBD. We also discuss epigenetics in IBD and the probiotic regulation of VDR. Furthermore, we discuss the existing challenges and future directions. There is a lack of well-designed clinical trials exploring the appropriate dose and the influence of gender, age, ethnicity, genetics, microbiome, and metabolic disorders in IBD subtypes. To move forward, we need well-designed therapeutic studies to examine whether enhanced vitamin D will restore functions of VDR and microbiome in inhibiting chronic inflammation.

scholarly journals The role of the microbiota in acute stress-induced myeloid immune cell trafficking

2020 ◽  
Vol 84 ◽  
pp. 209-217 ◽  
Author(s):  
Marcel van de Wouw ◽  
Joshua M. Lyte ◽  
Marcus Boehme ◽  
Marzia Sichetti ◽  
Gerard Moloney ◽  
...  
Keyword(s):  
Immune Cell ◽  
Acute Stress ◽  
Cell Trafficking ◽  
Immune Cell Trafficking

Gut Mycobiota and Fungal Metabolites in Human Homeostasis

2018 ◽  
Vol 20 (2) ◽  
pp. 232-240 ◽  
Author(s):  
Izabella Mogilnicka ◽  
Marcin Ufnal
Keyword(s):  
Wide Spectrum ◽  
Biological Effects ◽  
Fungal Species ◽  
Fungal Metabolites ◽  
Human Gut ◽  
Fecal Transplantation ◽  
Bacterial Microbiota ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Background:Accumulating evidence suggests that microbiota play an important role in host’s homeostasis. Thus far, researchers have mostly focused on the role of bacterial microbiota. However, human gut is a habitat for several fungal species, which produce numerous metabolites. Furthermore, various types of food and beverages are rich in a wide spectrum of fungi and their metabolites.Methods:We searched PUBMED and Google Scholar databases to identify clinical and pre-clinical studies on fungal metabolites, composition of human mycobiota and fungal dysbiosis.Results:Fungal metabolites may serve as signaling molecules and exert significant biological effects including trophic, anti-inflammatory or antibacterial actions. Finally, research suggests an association between shifts in gut fungi composition and human health. Changes in mycobiota composition have been found in obesity, hepatitis and inflammatory bowel diseases.Conclusion:The influence of mycobiota and dietary fungi on homeostasis in mammals suggests a pharmacotherapeutic potential of modulating the mycobiota which may include treatment with probiotics and fecal transplantation. Furthermore, antibacterial action of fungi-derived molecules may be considered as a substitution for currently used antibacterial agents and preservatives in food industry.

Role of MicroRNAs in Colon Cancer Progression and Metastasis

2020 ◽  
Vol 20 ◽  
Author(s):  
Shruthi Sanjitha Sampath ◽  
Sivaramakrishnan Venkatabalsubramanian ◽  
Satish Ramalingam
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Target Genes ◽  
Tumour Progression ◽  
Intestinal Barrier ◽  
Colon Cancer Progression ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Novel Therapeutic Strategies

: MicroRNAs regulate gene expression at the posttranscriptional level by binding to the mRNA of their target genes. The dysfunction of miRNAs is strongly associated with the inflammation of the colon. Besides, some microRNAs are shown to suppress tumours while others promote tumour progression and metastasis. Inflammatory bowel diseases include Crohn’s disease and Ulcerative colitis which increase the risk factor for inflammation-associated colon cancer. MicroRNAs are shown to be involved in gastrointestinal pathologies, by targeting the transcripts encoding proteins of the intestinal barrier and their regulators that are associated with inflammation and colon cancer. Detection of these microRNAs in the blood, serum, tissues, faecal matter, etc will enable us to use these microRNAs as biomarkers for early detection of the associated malignancies and design novel therapeutic strategies to overcome the same. Information on MicroRNAs can be applied for the development of targeted therapies against inflammation-mediated colon cancer.

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