Immune Netw.  2019 Aug;19(4):e27. 10.4110/in.2019.19.e27.

Intravenous Immunoglobulin Controls Th17 Cell-Mediated Osteoclastogenesis

• Kim KW
• Kim HR
• Kim BM
• Won JY
• Lee KA
• Lee SH

• KMID: 2455937
• DOI: http://doi.org/10.4110/in.2019.19.e27

Abstract

The purpose of this study was to determine the regulatory role of intravenous Ig (IVIg) in Th17 cytokine-induced RANK ligand (RANKL) expression and osteoclast (OC) differentiation from OC precursors (pre-OC). Human CD14⁺ monocytes were isolated and stimulated by Th17 cytokines (IL-17, IL-21, and IL-22) and RANKL expression was investigated using a real-time PCR. CD14⁺ monocytes were incubated with RANKL, Th17 cytokines, and M-CSF, with/without IVIg, and OC differentiation was determined by counting tartrate-resistant acid phosphatase-positive multinucleated cells. OC differentiation was investigated after monocytes were cocultured with Th17 cells in the presence of IVIg. Th17 cell differentiation was determined using enzyme-linked immunosorbent assay and flow cytometry after CD4⁺ T cells were cultured with IVIg under Th17 condition. Th17 cytokines stimulated monocytes to express RANKL and IVIg suppressed the Th17 cytokine-induced RANKL expression. OCs were differentiated when pre-OC were cocultured with RANKL or Th17 cytokines and IVIg reduced the osteoclastogenesis. IVIg also decreased osteoclastogenesis when pre-OC were cocultured with Th17 cells. IVIg decreased both Th17 and Th1 cell differentiation while it did not affect Treg cell differentiation. In summary, IVIg inhibited Th17 cytokine-induced RANKL expression and OC differentiation. IVIg reduced osteoclastogenesis when monocytes were cocultured with Th17 cells. IVIg also reduced Th17 polarization. IVIg could be a new therapeutic option for Th17 cell-mediated osteoclastogenesis.

Keyword

IVIg; Osteoclastogenesis; RANK ligand; IL-17; Th17 cells

MeSH Terms

Cytokines
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Humans
Immunoglobulins*
Immunoglobulins, Intravenous
Interleukin-17
Macrophage Colony-Stimulating Factor
Monocytes
Osteoclasts
RANK Ligand
Real-Time Polymerase Chain Reaction
T-Lymphocytes
T-Lymphocytes, Regulatory
Th1 Cells
Th17 Cells
Cytokines
Immunoglobulins
Immunoglobulins, Intravenous
Interleukin-17
Macrophage Colony-Stimulating Factor
RANK Ligand