Neutrophils-a new problem for MS

Rumble JM, Huber AK, Krishnamoorthy G, Srinivasan A, Giles DA, Zhang X, Wang L, Segal BM. Neutrophil-related factors as biomarkers in EAE and MS. J Exp Med. 2015 . pii: jem.20141015. [Epub ahead of print]

A major function of T helper (Th) 17 cells is to induce the production of factors that activate and mobilize neutrophils. Although Th17 cells have been implicated in the pathogenesis of multiple sclerosis (MS) and the animal model experimental autoimmune encephalomyelitis (EAE), little attention has been focused on the role of granulocytes in those disorders. 

We show that neutrophils, as well as monocytes, expand in the bone marrow and accumulate in the circulation before the clinical onset of EAE, in response to systemic up-regulation of granulocyte colony-stimulating factor (G-CSF) and the chemokine CXCL1. Neutrophils comprised a relatively high percentage of leucocytes infiltrating the central nervous system (CNS) early in disease development. G-CSF receptor deficiency and CXCL1 blockade suppressed myeloid cell accumulation in the blood and ameliorated the clinical course of mice that were injected with myelin-reactive Th17 cells. 

In relapsing MS patients, plasma levels of CXCL5 chemokine, were elevated during acute lesion formation. Systemic expression of CXCL1, CXCL5, and neutrophil elastase correlated with measures of MS lesion burden and clinical disability. Based on these results, we advocate that neutrophil-related molecules be further investigated as novel biomarkers and therapeutic targets in MS.

When first started MS research I was told that MS was a mononuclear (lymphocytes and macrophges) cell driven and that it was a white matter disease. So these bubbles get burst.

In mice it was always obvious that neutrophils were present in Lesions. In the HA mouse there were about 80% neutrophils in EAE lesions, in the ABH mouse there was less than 5% neutrophils, but they were within the cerebrospinal fluid. Immunology 101 of yesteryear said that mouse delayed hypersensititivty (T cell mediated allergic responses) reactions contained neutrophils which were not particularly common in rat or guinea pig EAE or MS.

In the C57BL/6 mouse it has recently been reported that TH17 T cells transfer EAE that is often atypical and causing disease in the cerebellum and having disease that contains neutrohils, compared to mononuclear cells in TH1 EAE.

In this study they find attractive proteins that attract neurtophils were present in the blood of MSers. Maybe they are important. It would be interesting to examine the effects in neuromyelitis optica, a demyelinating disease of optic nerve and spinal cord, where neutrophils are a problem.

Are neutrophils a big problem or is this reverse engineering to find something common in mice to show it is important in MS?

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