Bone marrow CD11b+F4/80+ dendritic cells ameliorate collagen-induced arthritis through modulating the balance between Treg and Th17

Lingling Zhang, Jingjing Fu, Kangliang Sheng, Ying Li, Shanshan Song, Peipei Li, Shasha Song, Qingtong Wang, Jingyu Chen, Jianhua Yu, Wei Wei

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Tolerogenic dendritic cells (DCs) are well-known to show an immunosuppressive function. In this study we determine the therapeutic effects and potential mechanisms of transferred bone marrow (BM) CD11b+F4/80+ DCs on collagen-induced arthritis (CIA) in mice. Murine BM CD11b+F4/80+ DCs were generated under the stimulation of GM-CSF and IL-4, and the function of BM CD11b+ F4/80+ DCs was identified by measuring the levels of IL-10, TGF-beta and indoleamine 2,3-dioxygenase (IDO). BM CD11b+F4/80+ DCs were transferred to CIA mice by intravenous injections. The histopathology of joint and spleen were evaluated. T lymphocyte proliferation, Treg and Th17 subsets were analyzed. The expressions of Foxp3, Helios and RORγt in T lymphocytes co-cultured with BM CD11b+F4/80+ DCs were measured in vitro. We found that BM CD11b+F4/80+ DCs induced by GM-CSF and IL-4 could express high levels of IL-10, TGF-beta and IDO. BM CD11b+F4/80+ DCs significantly reduced the pathologic scores in joints and spleens, which correlated significantly with the reduced T lymphocyte proliferation and Th17 cell number, and with the increased Tregs number. In vitro, OVA-pulsed BM CD11b+F4/80+ DCs promoted Treg cell expansion, enhanced IL-10 and CTLA-4 protein expression, augmented Foxp3 and Helios mRNA expression, and inhibited RORγt and IL-17 mRNA expression. Taken together, BM CD11b+F4/80+ DCs are able to ameliorate the development and severity of CIA, at least partly by inducing Foxp3+ Treg cell expansion and suppressing Th17 function. The BM CD11b+F4/80+ DCs might have a promising immunotherapeutic potential for autoimmune arthritis.

Original languageEnglish (US)
Pages (from-to)96-105
Number of pages10
JournalInternational Immunopharmacology
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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Keywords

  • Collagen induced arthritis
  • Dendritic cells
  • Foxp3 Treg
  • Rheumatoid arthritis
  • Th17

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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