title: Thymosin-α1 expands deficient IL-10-producing regulatory B cell subsets in relapsing-remitting multiple sclerosis patients.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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 CD19+CD24+CD38hitransitional-immature and CD24low/negCD38hiplasmablast-like regulatory B cell subsets, which likely inhibit both interferon (IFN)-γ and IL-17 production.
  
  
  
  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.
authors.affiliation: Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Giacomini
authors.affiliation: Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Rizzo
authors.affiliation: Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Marilena P
authors.initials: MP
authors.lastname: Etna
authors.affiliation: Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Melania
authors.initials: M
authors.lastname: Cruciani
authors.affiliation: Centre for Experimental Neurological Therapies (CENTERS), Sapienza University of Rome, Rome, Italy.
authors.forename: Rosella
authors.initials: R
authors.lastname: Mechelli
authors.affiliation: Centre for Experimental Neurological Therapies (CENTERS), Sapienza University of Rome, Rome, Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Buscarinu
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pica
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy/Clinical Microbiology Laboratories, Tor Vergata Hospital, Rome, Italy.
authors.forename: Cartesio
authors.initials: C
authors.lastname: D'Agostini
authors.affiliation: Centre for Experimental Neurological Therapies (CENTERS), Sapienza University of Rome, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Salvetti
authors.affiliation: Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Eliana M
authors.initials: EM
authors.lastname: Coccia
authors.affiliation: Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Severa
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D060151:B-Lymphocytes, Regulatory / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood*; D000077596:Thymalfasin / Q000097:blood* / Q000494:pharmacology*; D051199:Toll-Like Receptor 7 / Q000819:agonists; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; C508609:IL10 protein, human; D051199:Toll-Like Receptor 7; D016753:Interleukin-10; D000077596:Thymalfasin
keywords: B-lymphocytes; Multiple sclerosis; regulatory; thymosin alpha1