Crosstalk among IL-23 and DNAX activating protein of 12 kDa-Dependent pathways promotes osteoclastogenesis

Hyun Seock Shin, Ritu Sarin, Neha Dixit, Jian Wu, M. Eric Gershwin, Edward P. Bowman, Iannis Adamopoulos

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)316-324
Number of pages9
JournalJournal of Immunology
Volume194
Issue number1
DOIs
StatePublished - Jan 1 2015

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Interleukin-23
Osteogenesis
Osteoclasts
Myeloid Cells
Proteins
Cell Differentiation
Phospholipases
NF-kappa B
Lectins
Arthritis
Transcription Factors
Macrophages
Phosphorylation
Ligands
Calcium
T-Lymphocytes

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 journalArticle

Shin, Hyun Seock ; Sarin, Ritu ; Dixit, Neha ; Wu, Jian ; Gershwin, M. Eric ; Bowman, Edward P. ; Adamopoulos, Iannis. / Crosstalk among IL-23 and DNAX activating protein of 12 kDa-Dependent pathways promotes osteoclastogenesis. In: Journal of Immunology. 2015 ; Vol. 194, No. 1. pp. 316-324.
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