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Posted On: 03/02/2021 5:19:26 PM
Post# of 154704
Z_smith
The interaction that signals the activated T cells is CCL4-CCR5. The way I understand it, quick-and-dirty is that (VX) will antagonize the RANTES-CCR5 axis increasing the CCL4-CCR5 interactions. This is turn will restore homeostasis meaning more CCL4
From Agrestis's paper,
https://www.sciencedirect.com/science/article...034#bbib40
In a landmark study, Chua et al described lung epithelium and immune cell interactions and concluded that pharmacological inhibition of either the C–C chemokine receptor type 1 (CCR1) or CCR5 pathways may restore immune homeostasis
Chua et-al paper, depicts in more detail how this is concluded.
https://www.nature.com/articles/s41587-020-0602-4
I believe he is saying that, mainly, the reduction of CCL4-mediated recruitment is what is producing the LH symptoms. If there were more recruitment of T activated cells the virus would be cleared as the required inflammatory response is already present (elevated IFN-a).
Quote:
One part that I didn't quite understand is how does CCR5 antagonism yield an increase in CCL4?
The interaction that signals the activated T cells is CCL4-CCR5. The way I understand it, quick-and-dirty is that (VX) will antagonize the RANTES-CCR5 axis increasing the CCL4-CCR5 interactions. This is turn will restore homeostasis meaning more CCL4
From Agrestis's paper,
https://www.sciencedirect.com/science/article...034#bbib40
In a landmark study, Chua et al described lung epithelium and immune cell interactions and concluded that pharmacological inhibition of either the C–C chemokine receptor type 1 (CCR1) or CCR5 pathways may restore immune homeostasis
Chua et-al paper, depicts in more detail how this is concluded.
https://www.nature.com/articles/s41587-020-0602-4
Quote:
And I also didn't understand Dr. BP's statement "a reduction on the CCL4-mediated recruitment of activated T cells is proposed". I thought the goal was to increase CCL4 and thus increase the recruitment of activated T cells???
I believe he is saying that, mainly, the reduction of CCL4-mediated recruitment is what is producing the LH symptoms. If there were more recruitment of T activated cells the virus would be cleared as the required inflammatory response is already present (elevated IFN-a).
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