Immunomodulation of RA Patients’ PBMC with a Multiepitope Peptide Derived from Citrullinated Autoantigens

Autor: Yehuda Shoenfeld, Martin Cornillet, Sivan Vainer, Gidi Karmon, Smadar Gertel, Ora Shovman, Howard Amital, Guy Serre
Přispěvatelé: Chaim Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Tel Aviv University (TAU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CARBILLET, Véronique
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
MESH: Fibrinogen / metabolism
MESH: Collagen Type II / metabolism
MESH: Arthritis
Rheumatoid / drug therapy
Filaggrin Proteins
Autoantigens
Epitope
Arthritis
Rheumatoid
Epitopes
MESH: Autoantigens / therapeutic use
0302 clinical medicine
MESH: Arthritis
Rheumatoid / immunology
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
MESH: Synovial Membrane / drug effects
MESH: Aged
MESH: Middle Aged
biology
Chemistry
Synovial Membrane
FOXP3
Citrullination
Middle Aged
MESH: Autoantibodies / metabolism
3. Good health
MESH: Young Adult
[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
MESH: Autoantigens / immunology
Female
Antibody
Research Article
Filaggrin
lcsh:RB1-214
Adult
MESH: Leukocytes
Mononuclear / metabolism
MESH: Epitopes
Article Subject
CD3
Immunology
MESH: Autoantibodies / immunology
MESH: Autoantigens / chemistry
Proinflammatory cytokine
Immunomodulation
Young Adult
03 medical and health sciences
MESH: Immunomodulation / physiology
lcsh:Pathology
Humans
Vimentin
Collagen Type II
Aged
Autoantibodies
030203 arthritis & rheumatology
MESH: Vimentin / metabolism
MESH: Humans
Autoantibody
Fibrinogen
MESH: Adult
MESH: Synovial Membrane / metabolism
Cell Biology
MESH: Male
MESH: Leukocytes
Mononuclear / drug effects
030104 developmental biology
Leukocytes
Mononuclear
biology.protein
MESH: Citrullination
MESH: Female
Zdroj: Mediators of Inflammation, Vol 2017 (2017)
Mediators of Inflammation
Mediators of Inflammation, Hindawi Publishing Corporation, 2017, 2017, 9 p. ⟨10.1155/2017/3916519⟩
Mediators of Inflammation, 2017, 2017, 9 p. ⟨10.1155/2017/3916519⟩
ISSN: 1466-1861
0962-9351
Popis: Citrullinated peptides are used for measuring anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA). Accumulation of citrullinated proteins in the inflamed synovium suggests that they may be good targets for inducing peripheral tolerance. In view of the multiplicity of citrullinated autoantigens described as ACPA targets, we generated a multiepitope citrullinated peptide (Cit-ME) from the sequences of major citrullinated autoantigens: filaggrin, β-fibrinogen, vimentin, and collagen type II. We assessed the ability of Cit-ME or the citrullinated β60-74 fibrinogen peptide (β60-74-Fib-Cit) which bears immunodominant citrullinated epitopes (i) to modify cytokine gene expression and (ii) to modulate Treg and Th17 subsets in PBMC derived from newly diagnosed untreated RA patients. RA patient’s PBMC incubated with Cit-ME or β60-74-Fib-Cit, showed upregulation of TGF-β expression (16% and 8%, resp.), and increased CD4+Foxp3+ Treg (22% and 19%, resp.). Both peptides were shown to downregulate the TNF-α and IL-1β expression; in addition, Cit-ME reduced CD3+IL17+ T cells. We showed that citrullinated peptides can modulate the expression of anti- and proinflammatory cytokines in PBMC from RA patients as well as the proportions of Treg and Th17 cells. These results indicate that citrullinated peptides could be active in vivo and therefore might be used as immunoregulatory agents in RA patients.
Databáze: OpenAIRE
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