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 language | English (US) |
|---|---|
| Pages (from-to) | 96-105 |
| Number of pages | 10 |
| Journal | International Immunopharmacology |
| Volume | 25 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2015 |
| Externally published | Yes |
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Keywords
- Collagen induced arthritis
- Dendritic cells
- Foxp3 Treg
- Rheumatoid arthritis
- Th17
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Pharmacology
Cite this
Bone marrow CD11b+F4/80+ dendritic cells ameliorate collagen-induced arthritis through modulating the balance between Treg and Th17. / Zhang, Lingling; Fu, Jingjing; Sheng, Kangliang; Li, Ying; Song, Shanshan; Li, Peipei; Song, Shasha; Wang, Qingtong; Chen, Jingyu; Yu, Jianhua; Wei, Wei.
In: International Immunopharmacology, Vol. 25, No. 1, 01.01.2015, p. 96-105.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Bone marrow CD11b+F4/80+ dendritic cells ameliorate collagen-induced arthritis through modulating the balance between Treg and Th17
AU - Zhang, Lingling
AU - Fu, Jingjing
AU - Sheng, Kangliang
AU - Li, Ying
AU - Song, Shanshan
AU - Li, Peipei
AU - Song, Shasha
AU - Wang, Qingtong
AU - Chen, Jingyu
AU - Yu, Jianhua
AU - Wei, Wei
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
KW - Collagen induced arthritis
KW - Dendritic cells
KW - Foxp3 Treg
KW - Rheumatoid arthritis
KW - Th17
UR - http://www.scopus.com/inward/record.url?scp=84921863203&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84921863203&partnerID=8YFLogxK
U2 - 10.1016/j.intimp.2015.01.014
DO - 10.1016/j.intimp.2015.01.014
M3 - Article
VL - 25
SP - 96
EP - 105
JO - International Immunopharmacology
JF - International Immunopharmacology
SN - 1567-5769
IS - 1
ER -