Resolvin D5 Modulates Th17/Treg Cell Differentiation and Suppresses Osteoclastogenesis.

Abstract Resolvins, are specialized pro-resolving mediators (SPMs) derived from n-3 polyunsaturated fatty acids. They contribute actively to the resolution of inflammation, but little is known concerning their role in chronic inflammation, such as in rheumatoid arthritis (RA). Here, we performed lipid mediator (LM) profiling in tissues from the paws of SKG arthritic mice using lipid chromatography (LC) /mass spectrometry (MS) /MS-based LM metabololipidomics. We found elevated levels of SPMs including resolvin D5 (RvD5) in these tissues. Moreover, RvD5 levels were significantly correlated with arthritis disease activity. From experiments to assess the role of RvD5 in the pathology of RA, we concluded that RvD5 suppressed Th17 cell differentiation and facilitated regulatory T cell differentiation, as well as inhibiting CD4+ T cell proliferation. Furthermore, RvD5 attenuated osteoclast (OC) differentiation and interfered with osteoclastogenesis. Targeting the resolution of inflammation could be promising as a novel treatment for RA.

Download Full-text

Effect of resolvin D5 on T cell differentiation and osteoclastogenesis analyzed by lipid mediator profiling in the experimental arthritis

Scientific Reports ◽

10.1038/s41598-021-96530-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hirotaka Yamada ◽

Jun Saegusa ◽

Sho Sendo ◽

Yo Ueda ◽

Takaichi Okano ◽

...

Keyword(s):

Cell Differentiation ◽

T Cell ◽

Osteoclast Differentiation ◽

T Cell Differentiation ◽

T Cell Proliferation ◽

Lipid Mediator ◽

Resolution Of Inflammation ◽

Novel Treatment ◽

Th17 Cell Differentiation

AbstractResolvins, are specialized pro-resolving mediators (SPMs) derived from n-3 polyunsaturated fatty acids. They contribute actively to the resolution of inflammation, but little is known concerning their role in chronic inflammation, such as in rheumatoid arthritis (RA). Here, we performed lipid mediator (LM) profiling in tissues from the paws of SKG arthritic mice using lipid chromatography (LC)/mass spectrometry (MS)/MS-based LM metabololipidomics. We found elevated levels of SPMs including resolvin D5 (RvD5) in these tissues. Moreover, RvD5 levels were significantly correlated with arthritis disease activity. From experiments to assess the role of RvD5 in the pathology of RA, we concluded that RvD5 suppressed Th17 cell differentiation and facilitated regulatory T cell differentiation, as well as inhibiting CD4+ T cell proliferation. Furthermore, RvD5 attenuated osteoclast differentiation and interfered with osteoclastogenesis. Targeting the resolution of inflammation could be promising as a novel treatment for RA.

Download Full-text

Dichloroacetate induces regulatory T-cell differentiation and suppresses Th17-cell differentiation by pyruvate dehydrogenase kinase-independent mechanism

Journal of Pharmacy and Pharmacology ◽

10.1111/jphp.12655 ◽

2016 ◽

Vol 69 (1) ◽

pp. 43-51 ◽

Cited By ~ 8

Author(s):

Naoyuki Makita ◽

Jun Ishiguro ◽

Keisuke Suzuki ◽

Futoshi Nara

Keyword(s):

Cell Differentiation ◽

T Cell ◽

Pyruvate Dehydrogenase ◽

Regulatory T Cell ◽

Th17 Cell ◽

T Cell Differentiation ◽

Pyruvate Dehydrogenase Kinase ◽

Th17 Cell Differentiation ◽

Independent Mechanism

Download Full-text

Role of CD5 expression on TCRγδ T cell-differentiation and development of chronic intestinal inflammation

Gastroenterology ◽

10.1016/s0016-5085(01)82566-x ◽

2001 ◽

Vol 120 (5) ◽

pp. A517-A517

Author(s):

A MIZOGUCHI ◽

E MIZOGUCHI ◽

Y DEJONG ◽

H TAKEDATSU ◽

F PREFFER ◽

...

Keyword(s):

Cell Differentiation ◽

T Cell ◽

Intestinal Inflammation ◽

T Cell Differentiation ◽

Chronic Intestinal Inflammation

Download Full-text

The role of thymic accessory cells in cytokine production and in the intra-thymic T cell differentiation pathway

Memórias do Instituto Oswaldo Cruz ◽

10.1590/s0074-02761987000600006 ◽

1987 ◽

Vol 82 (suppl 2) ◽

pp. 23-28

Author(s):

Martine Papiernik

Keyword(s):

Cell Differentiation ◽

T Cell ◽

Cytokine Production ◽

T Cell Differentiation ◽

Accessory Cells

Download Full-text

Role of PD-1 during effector CD8 T cell differentiation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1718217115 ◽

2018 ◽

Vol 115 (18) ◽

pp. 4749-4754 ◽

Cited By ~ 92

Author(s):

Eunseon Ahn ◽

Koichi Araki ◽

Masao Hashimoto ◽

Weiyan Li ◽

James L. Riley ◽

...

Keyword(s):

T Cells ◽

Cell Differentiation ◽

T Cell ◽

Viral Infection ◽

Cd8 T Cells ◽

Cell Epitope ◽

Cd8 T Cell ◽

T Cell Differentiation ◽

Lcmv Infection

PD-1 (programmed cell death-1) is the central inhibitory receptor regulating CD8 T cell exhaustion during chronic viral infection and cancer. Interestingly, PD-1 is also expressed transiently by activated CD8 T cells during acute viral infection, but the role of PD-1 in modulating T cell effector differentiation and function is not well defined. To address this question, we examined the expression kinetics and role of PD-1 during acute lymphocytic choriomeningitis virus (LCMV) infection of mice. PD-1 was rapidly up-regulated in vivo upon activation of naive virus-specific CD8 T cells within 24 h after LCMV infection and in less than 4 h after peptide injection, well before any cell division had occurred. This rapid PD-1 expression by CD8 T cells was driven predominantly by antigen receptor signaling since infection with a LCMV strain with a mutation in the CD8 T cell epitope did not result in the increase of PD-1 on antigen-specific CD8 T cells. Blockade of the PD-1 pathway using anti–PD-L1 or anti–PD-1 antibodies during the early phase of acute LCMV infection increased mTOR signaling and granzyme B expression in virus-specific CD8 T cells and resulted in faster clearance of the infection. These results show that PD-1 plays an inhibitory role during the naive-to-effector CD8 T cell transition and that the PD-1 pathway can also be modulated at this stage of T cell differentiation. These findings have implications for developing therapeutic vaccination strategies in combination with PD-1 blockade.

Download Full-text