Mini-TrpRS is essential for IFNy-induced monocyte-derived giant cell formation

Journal Publication ResearchOnline@JCU
Biros, Erik;Vangaveti, Venkat;Moran, Corey
Venkat Vangaveti
Abstract

Truncated tryptophanyl-tRNA synthetase (mini-TrpRS), like any other aminoacyl-tRNA synthetases, canonically functions as a protein synthesis enzyme. Here we provide evidence for an additional signaling role of mini-TrpRS in the formation of monocyte-derived multinuclear giant cells (MGCs). Interferon-gamma (IFNγ) readily induced monocyte aggregation leading to MGC formation with paralleled marked upregulation of mini-TrpRS. Small interfering (si)RNA, targeting mini-TrpRS in the presence of IFNγ prevented monocyte aggregation. Moreover, blockade of mini-TrpRS, either by siRNA, or the cognate amino acid and decoy substrate D-Tryptophan to prevent mini-TrpRS signaling, resulted in a marked reduction in expression of the purinergic receptor P2X 7 (P2RX7) in monocytes activated by IFNγ. Our findings identify mini-TrpRS as a critical signaling molecule in a mechanism by which IFNγ initiates monocyte-derived giant cell formation.

Journal

Cytokine

Publication Name

Cytokine

Volume

142

ISBN/ISSN

1096-0023

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Pages Count

7

Location

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Publisher

Elsevier

Publisher Url

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Publisher Location

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Publish Date

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Url

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Date

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EISSN

N/A

DOI

10.1016/j.cyto.2021.155486