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© Research
Publication : Multiple sclerosis (Houndmills, Basingstoke, England)

Thymosin-α1 expands deficient IL-10-producing regulatory B cell subsets in relapsing-remitting multiple sclerosis patients

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Multiple sclerosis (Houndmills, Basingstoke, England) - 01 Feb 2017

Giacomini E, Rizzo F, Etna MP, Cruciani M, Mechelli R, Buscarinu MC, Pica F, D'Agostini C, Salvetti M, Coccia EM, Severa M

Link to Pubmed [PMID] – 28273784

Mult. Scler. 2018 Feb;24(2):127-139

BACKGROUND: B cells are key pathogenic effectors in multiple sclerosis (MS) and several therapies have been designed to restrain B cell abnormalities by directly targeting this lymphocyte population.

OBJECTIVES: Moving from our data showing a Toll-like receptor (TLR)7-driven dysregulation of B cell response in relapsing-remitting multiple sclerosis (RRMS) and having found a low serum level of Thymosin-α1 (Tα1) in patients, we investigated whether the addition of this molecule to peripheral blood mononuclear cells (PBMCs) would influence the expansion of regulatory B cell subsets, known to dampen autoimmune inflammation.

METHODS: Serum Tα1 level was measured by enzyme immunoassay. Cytokine expression was evaluated by Cytometric Bead Array (CBA), enzyme-linked immunosorbent assay (ELISA), and real-time reverse transcription polymerase chain reaction (RT-PCR). B cell subsets were analyzed by flow cytometry.

RESULTS: Tα1 pre-treatment induces an anti-inflammatory status in TLR7-stimulated RRMS PBMC cultures, reducing the secretion of pro-inflammatory interleukin (IL)-6, IL-8, and IL-1β while significantly increasing the regulatory IL-10 and IL-35. Indeed, Tα1 treatment enhanced expansion of CD19CD24CD38 transitional-immature and CD24CD38 plasmablast-like regulatory B cell subsets, which likely inhibit both interferon (IFN)-γ and IL-17 production.

CONCLUSION: Our study reveals a deficient ability of B cells from MS patients to differentiate into regulatory subsets and unveils a novel anti-inflammatory and repurposing potential for Tα1 in MS targeting B cell response.