Home News Recirculating Intestinal IgA-Producing Cells Regulate Neuroinflammation via IL-10

Recirculating Intestinal IgA-Producing Cells Regulate Neuroinflammation via IL-10

by Alessandro Leuti
Recirculating Intestinal IgA-Producing Cells Regulate Neuroinflammation via IL-10

B cells are involved in the pathogenesis of multiple sclerosis (MS) and, as a matter of fact, many drugs are designed to target CD20+ B cells as a treatment for this disease. However, many surprising evidences still suggest, to date, that our knowledge concerning the role of B cell axis in MS is still quite incomplete: for example, drugs targetting the plasma cells (PC) (the antibody-producing mature form of B cells) survival niches unexpectedly result in exacerbation of the disease. In light of these, more the involvement of antibody-secreting cells in immunomodulation during MS needs to be fully assessed. Interestingly, recent evidences show that IgA-producing PC possess antiinflammatory properties; plasma cells directed against tissue-specific antigens can be found way far from their mucosal origin and can be enriched in different organs, including the brain of MS patients. In light of this, Olga L. Rojas, Anne Katrin Probstel and Elisa A. Porfilio, as well as their many colleagues, sought to investigate a possible immunoregulatory role for  IgA-producing cells in multiple sclerosis.

The authors identified high numbers of IgA class-switched PC in the CNS of mice that underwent experimental autoimmune encephalomyelitis (EAE), both during the peak and the chronic phase of the disease, while absence of these cells resulted in exacerbated pathology, strongly suggesting that PC attempt to reduce inflammatory surges during the disease. The main source for these specific commensal-reactive IgA-producing cells was the gut. In a very elegant series of successive experiments, Rojas, Katrin and Porfilio proved that IgA-secreting PC egress the gut, where they are primarily generated, and recirculate in other organs, thus entering the brain where they suppress neuroinflammation in a IL-10-dependent manner: in order to prove so, the authors worked on a transgenic mouse line (BAFF-Tg mice) that is less susceptible to EAE and display higher numbers of gut-resident IgA-producing PC as well as commensal-reactive serum IgA. IL-10 -/- BAFF-Tg mice lose their resistance to the pathology and recover it upon adoptive transfer of gut-resident PC from healthy IL-10 producing BAFF-Tg littermates.

Source: Cell