Shoehorning man into mice is going to take us down the garden path.

S

A distinct mouse model of multiple sclerosis was used to examine factors involved in ectopic lymphoid tissue formation during central nervous system autoimmunity and eveals that infiltration and aggregation of B cells within the meninges is dependent upon B cell expression of VLA-4 and is preceded by neutrophil migration. This finding establishes the early mechanisms involved in the establishment of chronic inflammatory changes within the meninges during autoimmune inflammation that promote the formation of ectopic lymphoid tissue associated with disease progression and disability in multiple sclerosis. Is this cause and effect or are the they just co-incident observations. However the claim that this studies the early features of lesion change, is perhaps wishful thinking.

Neutrophils are the first line of defence against infection and are the most common white blood cells. In MS lesions they are noticable by their absence. In EAE in any other species bar a mouse, neutrophils do not seem to be common either. However, in some mouse strains they seem to be the dominant cell type and using these models it seems there is focus to shoehorn the human disease to become a mouse. If we continue to do this we will be looking in the wrong place.

neutrophils promote VLA-4-dependent B cell antigen presentation and accumulation within the meninges during neuroinflammation.Parker Harp CR, Archambault AS, Cheung M, Williams JW, Czepielewski RS, Duncker PC, Kilgore AJ, Miller AT, Segal BM, Kim AHJ, Randolph GJ, Wu GF. Proc Natl Acad Sci U S A. 2019 Nov 7. pii: 201909098

The success of B cell depletion therapies and identification of leptomeningeal ectopic lymphoid tissue (ELT) in patients with multiple sclerosis (MS) has renewed interest in the antibody-independent pathogenic functions of B cells during neuroinflammation. The timing and location of B cell antigen presentation during MS and its animal model experimental autoimmune encephalomyelitis (EAE) remain undefined. Using a new EAE system that incorporates temporal regulation of MHCII expression by myelin-specific B cells, we observed the rapid formation of large B cell clusters in the spinal cord subarachnoid space. Neutrophils preceded the accumulation of meningeal B cell clusters, and inhibition of CXCR2-mediated granulocyte trafficking to the central nervous system reduced pathogenic B cell clusters and disease severity. Further, B cell-restricted very late antigen-4 (VLA-4) deficiency abrogated EAE dependent on B cell antigen presentation. Together, our findings demonstrate that neutrophils coordinate VLA-4-dependent B cell accumulation within the meninges during neuroinflammation, a key early step in the formation of ELT observed in MS.

About the author

MouseDoctor

1 comment

  • “Neutrophils are the first line of defence against infection and are the most common white blood cells. In MS lesions they are noticable by their absence”

    Surprise surprise

    The often observed presence of neutrophils in the CSF of prepubertal patients suggests a prominent activation of the innate immune system, whereas the adaptive immune system usually becomes activated in postpubertal patients.4 In a subset of prepubertal MS patients, we observed neutrophils and eosinophils in low numbers within the lesions.

    Extensive Acute Axonal Damage in Pediatric Multiple Sclerosis Lesions

    doi:10.1002/ana.24364.

    🙂

By MouseDoctor

Translate

Categories

Recent Posts

Recent Comments

Archives