| Coordinating Panel on Rare Neurological Diseases  

Ataxin-1 regulates B cell function and the severity of autoimmune experimental encephalomyelitis.

Ataxin-1 regulates B cell function and the severity of autoimmune experimental encephalomyelitis.

www.pnas.org/cgi/doi/10.1073/pnas.2003798117

pubmed.ncbi.nlm.nih.gov/32878998/

 

Alessandro Didonnaa,1 Ester Canto Puiga, Qin Maa, Atsuko Matsunagaa, Brenda Hoa, Stacy J. Cailliera, Hengameh Shamsa, Nicholas Leea, Stephen L. Hausera, Qiumin Tan (谭秋敏)b, Scott S. Zamvila,c and Jorge R. Oksenberga
Ataxin-1 regulates B cell function and the severity of autoimmune experimental encephalomyelitis. 
www.pnas.org/cgi/doi/10.1073/pnas.2003798117
https://pubmed.ncbi.nlm.nih.gov/32878998/

This is an interesting work elucidating for the first time a role for ataxin-1 (ATXN1) mutation, traditionally linked to spinocerebellar ataxia-type 1 (SCA1), in the pathogenesis of Experimental Autoimmune Encephalomyelitis (EAE), the rodent model for Multiple Sclerosis (MS).  Recently ATXN1 has been identified as a susceptibility locus for MS. This paper shows that Atxn1-null mice develop a more severe EAE course compared to wildtype mice. In addition to the effect of Atxn1 ablation in resulting in T helper type 1 (Th1) cell polarization, this effect seems to be mediated by a caused dysregulation of the B cell activity, cells known to act as antigen-presenting cells towards T-cells.  As B-cells are recently identified, at least in part, as regulators of immune modulation and, therefore, as targets of pharmaceutical intervention also in progressive forms of MS, typically characterized by neurodegeneration, this paper highlights a previously understudied possible role of ataxin-1 also in immune-mediated neurodegenerative disease. 

 

References:

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2. H. Y. Zoghbi, H. T. Orr, Pathogenic mechanisms of a polyglutamine-mediated neu-rodegenerative disease, spinocerebellar ataxia type 1.J. Biol. Chem.284,7425–7429 (2009).
3. Y. C. Lamet al., ATAXIN-1 interacts with the repressor Capicua in its native complex tocause SCA1 neuropathology.Cell127, 1335–1347 (2006)