Is it me??? How does one, supposedly knowledgeable science writer pen a sentence like this and not have to explain the omission of LL, in such a study? It's not like there aren't clues all about the science environment.
The paper is about Chemokines. Not drugs. So therefore LL wouldn’t be discussed. The acceptance date of the paper seems to be Jan. 2020. But apart from a perceived snub to Leronlimab, here is a bit of a response to Riz’s original question about CCR5 deletion having no effect on MS.
“3.3. CCL5/Ccr5
CCL5 also has the name of RANTES, which is a marker for M1 macrophages. Infiltrating T cells are able to express and secrete che- mokine CCL5 [38], but CCL5 is mainly expressed in perivascular cells, vascular endothelial cells and astrocytes [31]. CCL5 is possible to adjust glutamate release and plasticity in the MS brain with associated effects for the disease clinical manifestations [79] and was detected in active demyelinated MS lesions. CCL5 and its receptor CCR5 have strong monocyte chemotaxis [92]. CCR5 is mainly expressed on immature dendritic cells, T cells, and a small number of monocytes [2] and is expressed on most monocytes, macrophages and CD8 + T cells in in- flammatory MS lesions [31]. There are two ways for CCR5 to be in- volved in the pathogenesis of MS. One is the increase in the number of CCR5-positive INF-γ-secreting T cells in the circulation of MS patients, and the other is that the monocytes having phagocytosis function greatly enriched CCR5 expression in CSF and peripheral blood [72].
In the research of E. Sindern et al., CCL5 was not detected in the CSF of RR-MS, but CCL5 release in serum was increased [107]. However, in the 2015 study by Mori F et al., including RRMS patients, CCL5 level was higher in CSF in patients than in the control group, and CCL5 in- creased during MS disease activity [79]. Other than that, one research by Sørensen et al. confirmed the presence of elevated CCL5 in cere- brospinal fluid in patients with acute MS and the fact that lymphocytes expressing CCR5 in the active MS lesions of autopsied brain tissue. The above pieces of evidence suggesting the role of CCL5 in the develop- ment of MS [107].
C57BL/6J mice infected with mouse hepatitis virus (MHV) in the brain can reproducibly result in acute encephalomyelitis and develop into chronic demyelinating disease. In the chronic disease stage, neu- ropathology is primarily immune-mediated, similar to human demye- linating disease MS (multiple sclerosis). Using this animal model, CCL5 is significantly expressed in the CNS during acute disease, and anti- CCL5 mAb-mediated neutralization results in delayed viral clearance with concomitant reduction of CCL5-induced migration of virus-specific T cells and activated macrophages, T cell and macrophage infiltration decreased and demyelination decreased. Experiments show that CCL5 contributes to macrophage entry and demyelination [38]. However, in another animal model, EAE model of MS, the immunological neu- tralization of CCL5 has no modulating effect. The use of DNA vacci- nation protocols to generate immunoneutralization antibodies against CCL5 also failed to inhibit disease induction in rat EAE(MOG induced in DA rats). CCR5 genomics deletion also did not protect EAE mice [30,96].
The impact of CCL5 genetic polymorphism (high producer allele) is relevant to the worse progression of MS disability, and low producer alleles are associated with a decreased risk of severe axonal loss [126]. The expression of CCL5 may be disrupted by gene mutations and
downregulation of its receptor CCR5. For example, a genetic poly- morphism, ie, a single nucleotide substitution (A to G) at 403 position of the CCL5 gene promoter results in lower expression of CCL5, or in the 303 position of its receptor CCR5 promoter sequence, X32 (32 base pair deletion) of CCR5 gene coding region is associated with a lower MS severity index [79]. Although a significant increase in CCR5 expression has been found in MS patients, it appears that besides the CCR5Δ32 mutation, other haplotypes or polymorphisms, as well as other possible epigenetic and genetic factors, are vital for CCR5 expression in multiple sclerosis patients [37]. In addition, based on a summary of one review, there appears to be no consensus on the association of CCR5Δ32 mu- tations with MS, and the differences in the reports may reflect the ge- netic background of the study population and their exposure to en- vironmental factors [37].
3.4. Ccl18
CCL18 also called alternative macrophage activation associated CC
The paper is about Chemokines. Not drugs. So therefore LL wouldn’t be discussed. The acceptance date of the paper seems to be Jan. 2020. But apart from a perceived snub to Leronlimab, here is a bit of a response to Riz’s original question about CCR5 deletion having no effect on MS.
“3.3. CCL5/Ccr5
CCL5 also has the name of RANTES, which is a marker for M1 macrophages. Infiltrating T cells are able to express and secrete che- mokine CCL5 [38], but CCL5 is mainly expressed in perivascular cells, vascular endothelial cells and astrocytes [31]. CCL5 is possible to adjust glutamate release and plasticity in the MS brain with associated effects for the disease clinical manifestations [79] and was detected in active demyelinated MS lesions. CCL5 and its receptor CCR5 have strong monocyte chemotaxis [92]. CCR5 is mainly expressed on immature dendritic cells, T cells, and a small number of monocytes [2] and is expressed on most monocytes, macrophages and CD8 + T cells in in- flammatory MS lesions [31]. There are two ways for CCR5 to be in- volved in the pathogenesis of MS. One is the increase in the number of CCR5-positive INF-γ-secreting T cells in the circulation of MS patients, and the other is that the monocytes having phagocytosis function greatly enriched CCR5 expression in CSF and peripheral blood [72].
In the research of E. Sindern et al., CCL5 was not detected in the CSF of RR-MS, but CCL5 release in serum was increased [107]. However, in the 2015 study by Mori F et al., including RRMS patients, CCL5 level was higher in CSF in patients than in the control group, and CCL5 in- creased during MS disease activity [79]. Other than that, one research by Sørensen et al. confirmed the presence of elevated CCL5 in cere- brospinal fluid in patients with acute MS and the fact that lymphocytes expressing CCR5 in the active MS lesions of autopsied brain tissue. The above pieces of evidence suggesting the role of CCL5 in the develop- ment of MS [107].
C57BL/6J mice infected with mouse hepatitis virus (MHV) in the brain can reproducibly result in acute encephalomyelitis and develop into chronic demyelinating disease. In the chronic disease stage, neu- ropathology is primarily immune-mediated, similar to human demye- linating disease MS (multiple sclerosis). Using this animal model, CCL5 is significantly expressed in the CNS during acute disease, and anti- CCL5 mAb-mediated neutralization results in delayed viral clearance with concomitant reduction of CCL5-induced migration of virus-specific T cells and activated macrophages, T cell and macrophage infiltration decreased and demyelination decreased. Experiments show that CCL5 contributes to macrophage entry and demyelination [38]. However, in another animal model, EAE model of MS, the immunological neu- tralization of CCL5 has no modulating effect. The use of DNA vacci- nation protocols to generate immunoneutralization antibodies against CCL5 also failed to inhibit disease induction in rat EAE(MOG induced in DA rats). CCR5 genomics deletion also did not protect EAE mice [30,96].
The impact of CCL5 genetic polymorphism (high producer allele) is relevant to the worse progression of MS disability, and low producer alleles are associated with a decreased risk of severe axonal loss [126]. The expression of CCL5 may be disrupted by gene mutations and
downregulation of its receptor CCR5. For example, a genetic poly- morphism, ie, a single nucleotide substitution (A to G) at 403 position of the CCL5 gene promoter results in lower expression of CCL5, or in the 303 position of its receptor CCR5 promoter sequence, X32 (32 base pair deletion) of CCR5 gene coding region is associated with a lower MS severity index [79]. Although a significant increase in CCR5 expression has been found in MS patients, it appears that besides the CCR5Δ32 mutation, other haplotypes or polymorphisms, as well as other possible epigenetic and genetic factors, are vital for CCR5 expression in multiple sclerosis patients [37]. In addition, based on a summary of one review, there appears to be no consensus on the association of CCR5Δ32 mu- tations with MS, and the differences in the reports may reflect the ge- netic background of the study population and their exposure to en- vironmental factors [37].
3.4. Ccl18
CCL18 also called alternative macrophage activation associated CC
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