title: Adoptive transfer of all-trans-retinal-induced regulatory T cells ameliorates experimental autoimmune arthritis in an interferon-gamma knockout model.
abstract: Maintaining an appropriate balance between subsets of CD4(+) helper T cells and T regulatory cells (Tregs) is a critical process in immune homeostasis and a protective mechanism against autoimmunity and inflammation. To identify the role of vitamin A-related compounds, we investigated the regulation of interleukin (IL)-17-producing helper T cells (Th17 cells) and Tregs treated with all-trans-retinal (retinal). CD4(+)T cells or total cells from the spleens of C57BL/6 mice were stimulated under Treg-polarizing (anti-CD3/CD28 and TGF-β) or Th17-polarizing (anti-CD3/CD28, TGF-β, and IL-6) conditions in the presence or absence of retinal. To analyze their suppressive abilities, retinal-induced Tregs or TGF-β-induced Tregs were co-cultured with responder T cells. Collagen-induced arthritis (CIA) was established in interferon (IFN)-γ knockout mice. On day 13, retinal-induced Tregs were adoptively transferred to mice with established CIA after second immunizations. Compared with TGF-β-induced Treg cells, retinal-induced Tregs showed increased Foxp3 expression and mediated stronger suppressive activity. Under Th17-polarizing conditions, retinal inhibited the production of IL-17 and increased the expression of Foxp3.Retinal-induced Tregs showed therapeutic effects in IFN-γ knockout CIA mice. Thus, we demonstrated that retinal reciprocally regulates Foxp3(+) Tregs and Th17 cells. These findings suggest that retinal, a vitamin A metabolite, can regulate the balance between pro- and anti-inflammatory immunity. A better understanding of the manipulation of Foxp3 and Tregs may enable the application of this tremendous therapeutic potential in various autoimmune diseases.
authors.affiliation: Laboratory of Immune Regulation, Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Jeon
authors.forename: Bo-Young
authors.initials: BY
authors.lastname: Yoon
authors.forename: Jung-Yeon
authors.initials: JY
authors.lastname: Lim
authors.forename: Hye-Jwa
authors.initials: HJ
authors.lastname: Oh
authors.forename: Hyun-Sil
authors.initials: HS
authors.lastname: Park
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Park
authors.forename: Mi-Ae
authors.initials: MA
authors.lastname: Lim
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Park
authors.forename: Kyung-Woon
authors.initials: KW
authors.lastname: Kim
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
authors.forename: Seok-Goo
authors.initials: SG
authors.lastname: Cho
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000628:therapy*; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics*; D020381:Interleukin-17 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012172:Retinaldehyde / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000637:transplantation*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D007371:Interferon-gamma; D012172:Retinaldehyde