Dysbiosis in gut microbiome has been shown to be associated with inflammatory and autoimmune diseases. Previous studies from our laboratory demonstrated the pivotal role played by CD44 in the regulation of experimental autoimmune encephalomyelitis (EAE), a murine (They mean mouse) model of multiple sclerosis (I bet the people doing marmoset studies would like to think they do EAE studies). In the current study, we determined whether these effects resulted from an alteration in gut microbiota in CD44KO mice (CD44 is a molecule on white blood cells that gets upregulated in memory T cells. This binds to hylauronic acid which gets deposited in lesions).
Feacal transfer from naïve CD44KO but not CD44WT mice, into EAE-induced CD44WT mice, led to significant amelioration of EAE.
High-throughput bacterial 16S rRNA gene sequencing and biochemical analysis, revealed that EAE-induced CD44KO mice showed significant diversity, richness, and evenness when compared to EAE-induced CD44WT mice at the phylum level, with dominant Bacteroidetes (68.5%) and low Firmicutes (26.8%).
In conclusion, our results demonstrate that the attenuation of EAE seen following CD44 gene deletion in mice may result from alterations in the gut microbiota. Furthermore, our studies also demonstrate that the phenotype of gene knock-out animals may be shaped by gut microbiota.
Brennan FR, O’Neill JK, Allen SJ, Butter C, Nuki G, Baker D.CD44 is involved in selective leucocyte extravasation during inflammatory central nervous system disease. Clinical signs of experimental autoimmune encephalomyelitis (EAE) are associated with the selective recruitment of CD4+ memory (CD45RBlow CD44high) T cells into the central nervous system (CNS). However, we have found that many of these recently recruited memory cells are CD44low, suggesting that the CD44 antigen may be involved in, and transiently lost during, the extravasation process. Indeed, administration of a CD44-specific antibody (IM7.8.1) induced leucocyte CD44 shedding and both prevented the development and ameliorated the severity of established EAE by inhibiting mononuclear cell infiltration into the CNS. Trafficking of cells into lymph nodes, however, a property mainly of naïve cells, was essentially unaffected. In contrast, treatment with antibody to very late activation antigen-4 (VLA-4) prevented homing to both the CNS and to lymph nodes. This study contests previous reports that dismissed a role for CD44 in inflammation of the CNS and, coupled with observations in murine dermatitis and arthritis, suggests that CD44 is involved in the homing of primed lymphocytes to sites of inflammation. CD44 should therefore be considered a target for immunotherapy of T-cell-mediated inflammatory diseases, such as multiple sclerosis.Immunology. 1999;98(3):427-35
Science is about re-interpretation of existing knowledge in the light of noew knowledge, so we re-invent the wheel, however I wonder if we sometimes make it square, when we pigeon-hole work into dogma
