Doug Dyer
@douglaspdyer.bsky.social
Immune cell recruitment, glycocalyx, chemokines and extracellular matrix at the Manchester Centre for Cell Matrix research and Lydia Becker Institute for Immunology he/him
https://www.wellcome-matrix.org/people/doug-dyer/
#glycotime
https://www.wellcome-matrix.org/people/doug-dyer/
#glycotime
This the lung micro environment regulates the macrophage glycocalyx via local cytokines at rest and following infection, a process likely crucial to viral infection
November 20, 2025 at 8:13 PM
This the lung micro environment regulates the macrophage glycocalyx via local cytokines at rest and following infection, a process likely crucial to viral infection
To fully determine the effect of the lung environment on the glycocalyx we transferred macrophages with low glycocalyx into the airways space and saw that this drove an increase in the transferred cells glycocalyx
November 20, 2025 at 8:13 PM
To fully determine the effect of the lung environment on the glycocalyx we transferred macrophages with low glycocalyx into the airways space and saw that this drove an increase in the transferred cells glycocalyx
Using an in vivo flu infection model we showed that the effect of type 1 cytokines is overridden by the lung environment, with alveolar and interstitial macrophages increasing their glycocalyx at 7 and 14 days post infection
November 20, 2025 at 8:13 PM
Using an in vivo flu infection model we showed that the effect of type 1 cytokines is overridden by the lung environment, with alveolar and interstitial macrophages increasing their glycocalyx at 7 and 14 days post infection
To verify the effect of type 1 cytokines on the macrophage glycocalyx we stimulated a macrophage cell line with the viral mimic poly I:C resulting in glycocalyx shed
November 20, 2025 at 8:13 PM
To verify the effect of type 1 cytokines on the macrophage glycocalyx we stimulated a macrophage cell line with the viral mimic poly I:C resulting in glycocalyx shed
She again probed this at the transcriptional level with very differential effects on genes that regulate the cell surfaces glycocalyx
November 20, 2025 at 8:13 PM
She again probed this at the transcriptional level with very differential effects on genes that regulate the cell surfaces glycocalyx
She then further polarised her macrophages with type 1 and 2 cytokines with contrasting effects on glycocalyx content
November 20, 2025 at 8:13 PM
She then further polarised her macrophages with type 1 and 2 cytokines with contrasting effects on glycocalyx content
Next she explored glycocalyx regulation by proving the effect of macrophages derived with M-CSF vs GM-CSF
November 20, 2025 at 8:13 PM
Next she explored glycocalyx regulation by proving the effect of macrophages derived with M-CSF vs GM-CSF
Zi first used imaging and flow cytometry to show that alveolar macrophages in the airways have a strong WGA detectable glycocalyx
November 20, 2025 at 8:13 PM
Zi first used imaging and flow cytometry to show that alveolar macrophages in the airways have a strong WGA detectable glycocalyx
Our proposed model is summarised here
October 29, 2025 at 5:23 PM
Our proposed model is summarised here
Finally with the help of @Hepworth_Lab we demonstrated this protective effect of recruited monocytes was via their regulation of ILC3 cytokine production
October 29, 2025 at 5:23 PM
Finally with the help of @Hepworth_Lab we demonstrated this protective effect of recruited monocytes was via their regulation of ILC3 cytokine production
We then used CCR2 deficient mice and monocyte transfer rescue experiments to demonstrate that CCR2 mediated monocyte recruitment is crucial to recovery from intestinal RT
October 29, 2025 at 5:23 PM
We then used CCR2 deficient mice and monocyte transfer rescue experiments to demonstrate that CCR2 mediated monocyte recruitment is crucial to recovery from intestinal RT
To determine which of these chemokine receptors might be responsible for this worsened response to RT we used the newly developed iCCR reporter mice elifesciences.org/articles/72418 Revealing CCR2 as a prime candidate
October 29, 2025 at 5:23 PM
To determine which of these chemokine receptors might be responsible for this worsened response to RT we used the newly developed iCCR reporter mice elifesciences.org/articles/72418 Revealing CCR2 as a prime candidate
We then observed that in mice that lack the iCCR receptors (CCR1, 2, 3 and 5) and cannot recruit monocytes and eosinophils, RT induced toxicity was surprisingly worsened pubmed.ncbi.nlm.nih.gov/30784579/
October 29, 2025 at 5:23 PM
We then observed that in mice that lack the iCCR receptors (CCR1, 2, 3 and 5) and cannot recruit monocytes and eosinophils, RT induced toxicity was surprisingly worsened pubmed.ncbi.nlm.nih.gov/30784579/
We next used single cell RNA sequencing and flow cytometry to demonstrate RT induced chemokine mediated immune cell recruitment to the small intestine in mice and that this is likely also the case in human bladder cancer patients receiving RT
October 29, 2025 at 5:23 PM
We next used single cell RNA sequencing and flow cytometry to demonstrate RT induced chemokine mediated immune cell recruitment to the small intestine in mice and that this is likely also the case in human bladder cancer patients receiving RT
We firstly set out to establish a model of localised radiation induced damage to the intestine resulting in weight loss and increased intestinal permeability
October 29, 2025 at 5:23 PM
We firstly set out to establish a model of localised radiation induced damage to the intestine resulting in weight loss and increased intestinal permeability
Our director @rachellennon.bsky.social on how we will achieve the future aims of the centre
June 25, 2025 at 2:56 PM
Our director @rachellennon.bsky.social on how we will achieve the future aims of the centre
Celebrating the 30th anniversary of the matrix centre today!!
June 25, 2025 at 12:07 PM
Celebrating the 30th anniversary of the matrix centre today!!
Celebrating an acceptance!
May 2, 2025 at 3:07 PM
Celebrating an acceptance!
Finally and very excitingly we re-produced previous work that CXCL4 promotes neurogenesis but showed this is GAG binding dependent where neurons have been shown to have lots of proetoglycans on their cell surface.
April 28, 2025 at 7:42 AM
Finally and very excitingly we re-produced previous work that CXCL4 promotes neurogenesis but showed this is GAG binding dependent where neurons have been shown to have lots of proetoglycans on their cell surface.
Injection of peripheral LPS had a significant but surprisingly subtle effect on this uptake form circulation to blood, unlike other chemokines CCL2 and CCL5.
April 28, 2025 at 7:42 AM
Injection of peripheral LPS had a significant but surprisingly subtle effect on this uptake form circulation to blood, unlike other chemokines CCL2 and CCL5.
Using the same approach we also showed that CXCL4 is rapidly cleared from the brain but remains bound to the vasculature for a long period of time.
April 28, 2025 at 7:42 AM
Using the same approach we also showed that CXCL4 is rapidly cleared from the brain but remains bound to the vasculature for a long period of time.
To confirm entry we used our cranial window imaging approach to analyse movement of fluorescent labelled CXCL4, showing entry into the brain, interaction with the vascular and excitingly potential interaction with neuronal structures…
April 28, 2025 at 7:42 AM
To confirm entry we used our cranial window imaging approach to analyse movement of fluorescent labelled CXCL4, showing entry into the brain, interaction with the vascular and excitingly potential interaction with neuronal structures…
To test this hypothesis we analysed wild type and mutant presence in vascular and parenchymal brain fractions, as hypothesised the WT was retained longer in the vasculature than the mutant, potentially enabling local signaling.
April 28, 2025 at 7:42 AM
To test this hypothesis we analysed wild type and mutant presence in vascular and parenchymal brain fractions, as hypothesised the WT was retained longer in the vasculature than the mutant, potentially enabling local signaling.
We then used in situ radio labeled studies to show CXCL4 and its mutant that doesn’t cross link GAG chains are rapidly cleared from the circulation and enter the brain. Surprisingly the mutant entered quicker due to its rapid dynamics allowing quicker release from the transporting proteoglycans.
April 28, 2025 at 7:42 AM
We then used in situ radio labeled studies to show CXCL4 and its mutant that doesn’t cross link GAG chains are rapidly cleared from the circulation and enter the brain. Surprisingly the mutant entered quicker due to its rapid dynamics allowing quicker release from the transporting proteoglycans.
We next investigated CXCL4 movement into the brain, firstly showing it can bind to GAGs on endothelial cells and used radio labeled tracer studies to show it can be enter the brain parenchyma in a GAG dependent fashion.
April 28, 2025 at 7:42 AM
We next investigated CXCL4 movement into the brain, firstly showing it can bind to GAGs on endothelial cells and used radio labeled tracer studies to show it can be enter the brain parenchyma in a GAG dependent fashion.