The glial cells play pivotal roles in the central nervous system (CNS) by supporting its development, maintaining homeostasis, producing myelin, and providing support and protection for neurons1. These cells are increasingly under scientific scrutiny in the pathogenesis of neurodegenerative disorders (ND).
The activated microglia, a subset of glial cells, have been demonstrated to be the main determinant of neuroinflammation that contributes to neurodegeneration2. Increasing evidence supports the interactions of various microorganisms with the human immune system in contributing (directly and indirectly) to the onset and severity of ND3.
In a recent attempt to determine the source and role of these cells in the CNS of MS patients, Gommerman and co-workers utilised multiple approaches, including the adoptive transfer experimental autoimmune encephalomyelitis (EAE) model, to elucidate their source and function, as well as clarify their associations to the microbiota in the CNS during neuroinflammation6.
They uncovered that some PCs in the CNS of EAE mice originate in the gut and produce immunoglobulin A (IgA). The presence of IgA+ PBs and PCs in the CNS was unexpected, given that IgA is principally produced and secreted at mucosal surfaces. In addition, the authors found that these gut-derived IgA+ B cells were able to attenuate inflammation in the CNS. Therefore, even though IgA-producing PC are well-known to produce copious anti-commensal antibodies in the gut during homeostasis, these new results should evoke an emendation of these cells during autoimmune and neuroinflammatory diseases.
However, in another study, Zhou et al. reported BAFF-Tg mice exhibited exacerbated EAE that correlated with increased Th17 cells in the draining lymph nodes8. These divergent results and reports suggest that distinct vivarium-associated microbiota, which is known to affect IgA+ antibody-secreting cells in the CNS, require further studies.
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The activated microglia, a subset of glial cells, have been demonstrated to be the main determinant of neuroinflammation that contributes to neurodegeneration2. Increasing evidence supports the interactions of various microorganisms with the human immune system in contributing (directly and indirectly) to the onset and severity of ND3.
Examining MS Pathogenesis in Mouse Models
Multiple sclerosis, the most frequent chronic inflammatory disease of the CNS, is a demyelinating disease of inexorable damage to the insulating protection of neurons within the central and peripheral nervous system (CNS and PNS)4,5. One important driver of MS pathogenesis and potential therapeutic target are the B-cells and their effector subsets, plasmablasts (PBs) and plasma cells (PCs).In a recent attempt to determine the source and role of these cells in the CNS of MS patients, Gommerman and co-workers utilised multiple approaches, including the adoptive transfer experimental autoimmune encephalomyelitis (EAE) model, to elucidate their source and function, as well as clarify their associations to the microbiota in the CNS during neuroinflammation6.
They uncovered that some PCs in the CNS of EAE mice originate in the gut and produce immunoglobulin A (IgA). The presence of IgA+ PBs and PCs in the CNS was unexpected, given that IgA is principally produced and secreted at mucosal surfaces. In addition, the authors found that these gut-derived IgA+ B cells were able to attenuate inflammation in the CNS. Therefore, even though IgA-producing PC are well-known to produce copious anti-commensal antibodies in the gut during homeostasis, these new results should evoke an emendation of these cells during autoimmune and neuroinflammatory diseases.
Does IL-10 Expression Ameliorate MS Symptoms?
Importantly, MS patients exhibited an abatement of fecal bacteria-bound IgA during relapses, possibly due to egress of IgA-producing cells from the gut. Gommerman's group discovered that the expression of IL-10 by PCs was integral for the amelioration of EAE, which were findings consistent with previous work by Matsumoto et al.7.However, in another study, Zhou et al. reported BAFF-Tg mice exhibited exacerbated EAE that correlated with increased Th17 cells in the draining lymph nodes8. These divergent results and reports suggest that distinct vivarium-associated microbiota, which is known to affect IgA+ antibody-secreting cells in the CNS, require further studies.
View the Taconic Biosciences' Webinar: