Abstract
IL-23 has been well studied in the context of T cell differentiation; however, its role in the differentiation ofmyeloid progenitors is less clear. In this paper, we describe a novel role of IL-23 in myeloid cell differentiation. Specifically, we have identified that in human PBMCs, IL-23 induces the expression of MDL-1, a PU.1 transcriptional target during myeloid differentiation, which orchestrates osteoclast differentiation through activation of DNAX activating protein of 12 kDa and its ITAMs. The molecular events that lead to the differentiation of human macrophages to terminally differentiated osteoclasts are dependent on spleen tyrosine kinase and phospholipase Cg2 phosphorylation for the induction of intracellular calcium flux and the subsequent activation of master regulator osteoclast transcription factor NFATc1. IL-23-elicited osteoclastogenesis is independent of the receptor activator of NF-kB ligand pathway and uses a unique myeloid DNAX activating protein of 12 kDa-associated lectin-1+/DNAX activating protein of 12 kDa+ cell subset. Our data define a novel pathway that is used by IL-23 in myeloid cells and identify a major mechanism for the stimulation of osteoclastogenesis in inflammatory arthritis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 316-324 |
| Number of pages | 9 |
| Journal | Journal of Immunology |
| Volume | 194 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2015 |
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ASJC Scopus subject areas
- Immunology
Cite this
Crosstalk among IL-23 and DNAX activating protein of 12 kDa-Dependent pathways promotes osteoclastogenesis. / Shin, Hyun Seock; Sarin, Ritu; Dixit, Neha; Wu, Jian; Gershwin, M. Eric; Bowman, Edward P.; Adamopoulos, Iannis.
In: Journal of Immunology, Vol. 194, No. 1, 01.01.2015, p. 316-324.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Crosstalk among IL-23 and DNAX activating protein of 12 kDa-Dependent pathways promotes osteoclastogenesis
AU - Shin, Hyun Seock
AU - Sarin, Ritu
AU - Dixit, Neha
AU - Wu, Jian
AU - Gershwin, M. Eric
AU - Bowman, Edward P.
AU - Adamopoulos, Iannis
PY - 2015/1/1
Y1 - 2015/1/1
N2 - IL-23 has been well studied in the context of T cell differentiation; however, its role in the differentiation ofmyeloid progenitors is less clear. In this paper, we describe a novel role of IL-23 in myeloid cell differentiation. Specifically, we have identified that in human PBMCs, IL-23 induces the expression of MDL-1, a PU.1 transcriptional target during myeloid differentiation, which orchestrates osteoclast differentiation through activation of DNAX activating protein of 12 kDa and its ITAMs. The molecular events that lead to the differentiation of human macrophages to terminally differentiated osteoclasts are dependent on spleen tyrosine kinase and phospholipase Cg2 phosphorylation for the induction of intracellular calcium flux and the subsequent activation of master regulator osteoclast transcription factor NFATc1. IL-23-elicited osteoclastogenesis is independent of the receptor activator of NF-kB ligand pathway and uses a unique myeloid DNAX activating protein of 12 kDa-associated lectin-1+/DNAX activating protein of 12 kDa+ cell subset. Our data define a novel pathway that is used by IL-23 in myeloid cells and identify a major mechanism for the stimulation of osteoclastogenesis in inflammatory arthritis.
AB - IL-23 has been well studied in the context of T cell differentiation; however, its role in the differentiation ofmyeloid progenitors is less clear. In this paper, we describe a novel role of IL-23 in myeloid cell differentiation. Specifically, we have identified that in human PBMCs, IL-23 induces the expression of MDL-1, a PU.1 transcriptional target during myeloid differentiation, which orchestrates osteoclast differentiation through activation of DNAX activating protein of 12 kDa and its ITAMs. The molecular events that lead to the differentiation of human macrophages to terminally differentiated osteoclasts are dependent on spleen tyrosine kinase and phospholipase Cg2 phosphorylation for the induction of intracellular calcium flux and the subsequent activation of master regulator osteoclast transcription factor NFATc1. IL-23-elicited osteoclastogenesis is independent of the receptor activator of NF-kB ligand pathway and uses a unique myeloid DNAX activating protein of 12 kDa-associated lectin-1+/DNAX activating protein of 12 kDa+ cell subset. Our data define a novel pathway that is used by IL-23 in myeloid cells and identify a major mechanism for the stimulation of osteoclastogenesis in inflammatory arthritis.
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U2 - 10.4049/jimmunol.1401013
DO - 10.4049/jimmunol.1401013
M3 - Article
VL - 194
SP - 316
EP - 324
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 1
ER -