Histidyl-tRNA synthetase and asparaginyl-tRNA synthetase, autoantigens in myositis, activate chemokine receptors on T lymphocytes and immature dendritic cells

O. M. Zack Howard, Hui Fang Dong, Yang De Yang, Nina Raben, Kanneboyina Nagaraju, Antony Rosen, Livia A Casciola Rosen, Michael Härtlein, Michael Kron, David Yang, Kwabena Yiadom, Sunita Dwivedi, Paul H. Plotz, Joost J. Oppenheim

Research output: Contribution to journalArticle

Abstract

Autoantibodies to histidyl-tRNA synthetase (HisRS) or to alanyl-, asparaginyl-, glycyl-, isoleucyl-, or threonyl-tRNA synthetase occur in ∼25% of patients with polymyositis or dermatomyositis. We tested the ability of several aminoacyl-tRNA synthetases to induce leukocyte migration. HisRS induced CD4 + and CD8 + lymphocytes, interleukin (IL)-2-activated monocytes, and immature dendritic cells (iDCs) to migrate, but not neutrophils, mature DCs, or unstimulated monocytes. An NH 2-terminal domain, 1-48 HisRS, was chemotactic for lymphocytes and activated monocytes, whereas a deletion mutant, HisRS-M, was inactive. HisRS selectively activated CC chemokine receptor (CCR)5-transfected HEK-293 cells, inducing migration by interacting with extracellular domain three. Furthermore, monoclonal anti-CCR5 blocked HisRS-induced chemotaxis and conversely, HisRS blocked anti-CCR5 binding. Asparaginyl-tRNA synthetase induced migration of lymphocytes, activated monocytes, iDCs, and CCR3-transfected HEK-293 cells. Seryl-tRNA synthetase induced migration of CCR3-transfected cells but not iDCs. Non-autoantigenic aspartyl-tRNA and lysyl-tRNA synthetases were not chemotactic. Thus, autoantigenic aminoacyl-tRNA synthetases, perhaps liberated from damaged muscle cells, may perpetuate the development of myositis by recruiting mononuclear cells that induce innate and adaptive immune responses. Therefore, the selection of a self-molecule as a target for an autoantibody response may be a consequence of the proinflammatory properties of the molecule itself.

Original languageEnglish (US)
Pages (from-to)781-791
Number of pages11
JournalJournal of Experimental Medicine
Volume196
Issue number6
DOIs
StatePublished - Sep 16 2002

Fingerprint

asparaginyl-tRNA synthetase
Histidine-tRNA Ligase
Myositis
Chemokine Receptors
Autoantigens
Dendritic Cells
T-Lymphocytes
Monocytes
Amino Acyl-tRNA Synthetases
HEK293 Cells
Lymphocytes
Autoantibodies
Threonine-tRNA Ligase
Serine-tRNA Ligase
Lysine-tRNA Ligase
CCR5 Receptors
Aptitude
Dermatomyositis
Adaptive Immunity
Chemotaxis

Keywords

  • Aminoacyl-tRNA synthetase
  • Autoantibody
  • Autoimmunity
  • Chemokine receptor
  • Myopathy

ASJC Scopus subject areas

  • Immunology

Cite this

Histidyl-tRNA synthetase and asparaginyl-tRNA synthetase, autoantigens in myositis, activate chemokine receptors on T lymphocytes and immature dendritic cells. / Zack Howard, O. M.; Dong, Hui Fang; De Yang, Yang; Raben, Nina; Nagaraju, Kanneboyina; Rosen, Antony; Casciola Rosen, Livia A; Härtlein, Michael; Kron, Michael; Yang, David; Yiadom, Kwabena; Dwivedi, Sunita; Plotz, Paul H.; Oppenheim, Joost J.

In: Journal of Experimental Medicine, Vol. 196, No. 6, 16.09.2002, p. 781-791.

Research output: Contribution to journalArticle

Zack Howard, OM, Dong, HF, De Yang, Y, Raben, N, Nagaraju, K, Rosen, A, Casciola Rosen, LA, Härtlein, M, Kron, M, Yang, D, Yiadom, K, Dwivedi, S, Plotz, PH & Oppenheim, JJ 2002, 'Histidyl-tRNA synthetase and asparaginyl-tRNA synthetase, autoantigens in myositis, activate chemokine receptors on T lymphocytes and immature dendritic cells', Journal of Experimental Medicine, vol. 196, no. 6, pp. 781-791. https://doi.org/10.1084/jem.20020186
Zack Howard, O. M. ; Dong, Hui Fang ; De Yang, Yang ; Raben, Nina ; Nagaraju, Kanneboyina ; Rosen, Antony ; Casciola Rosen, Livia A ; Härtlein, Michael ; Kron, Michael ; Yang, David ; Yiadom, Kwabena ; Dwivedi, Sunita ; Plotz, Paul H. ; Oppenheim, Joost J. / Histidyl-tRNA synthetase and asparaginyl-tRNA synthetase, autoantigens in myositis, activate chemokine receptors on T lymphocytes and immature dendritic cells. In: Journal of Experimental Medicine. 2002 ; Vol. 196, No. 6. pp. 781-791.
@article{967f159cf79245c99279f1493fa2751b,
title = "Histidyl-tRNA synthetase and asparaginyl-tRNA synthetase, autoantigens in myositis, activate chemokine receptors on T lymphocytes and immature dendritic cells",
abstract = "Autoantibodies to histidyl-tRNA synthetase (HisRS) or to alanyl-, asparaginyl-, glycyl-, isoleucyl-, or threonyl-tRNA synthetase occur in ∼25{\%} of patients with polymyositis or dermatomyositis. We tested the ability of several aminoacyl-tRNA synthetases to induce leukocyte migration. HisRS induced CD4 + and CD8 + lymphocytes, interleukin (IL)-2-activated monocytes, and immature dendritic cells (iDCs) to migrate, but not neutrophils, mature DCs, or unstimulated monocytes. An NH 2-terminal domain, 1-48 HisRS, was chemotactic for lymphocytes and activated monocytes, whereas a deletion mutant, HisRS-M, was inactive. HisRS selectively activated CC chemokine receptor (CCR)5-transfected HEK-293 cells, inducing migration by interacting with extracellular domain three. Furthermore, monoclonal anti-CCR5 blocked HisRS-induced chemotaxis and conversely, HisRS blocked anti-CCR5 binding. Asparaginyl-tRNA synthetase induced migration of lymphocytes, activated monocytes, iDCs, and CCR3-transfected HEK-293 cells. Seryl-tRNA synthetase induced migration of CCR3-transfected cells but not iDCs. Non-autoantigenic aspartyl-tRNA and lysyl-tRNA synthetases were not chemotactic. Thus, autoantigenic aminoacyl-tRNA synthetases, perhaps liberated from damaged muscle cells, may perpetuate the development of myositis by recruiting mononuclear cells that induce innate and adaptive immune responses. Therefore, the selection of a self-molecule as a target for an autoantibody response may be a consequence of the proinflammatory properties of the molecule itself.",
keywords = "Aminoacyl-tRNA synthetase, Autoantibody, Autoimmunity, Chemokine receptor, Myopathy",
author = "{Zack Howard}, {O. M.} and Dong, {Hui Fang} and {De Yang}, Yang and Nina Raben and Kanneboyina Nagaraju and Antony Rosen and {Casciola Rosen}, {Livia A} and Michael H{\"a}rtlein and Michael Kron and David Yang and Kwabena Yiadom and Sunita Dwivedi and Plotz, {Paul H.} and Oppenheim, {Joost J.}",
year = "2002",
month = "9",
day = "16",
doi = "10.1084/jem.20020186",
language = "English (US)",
volume = "196",
pages = "781--791",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "6",

}

TY - JOUR

T1 - Histidyl-tRNA synthetase and asparaginyl-tRNA synthetase, autoantigens in myositis, activate chemokine receptors on T lymphocytes and immature dendritic cells

AU - Zack Howard, O. M.

AU - Dong, Hui Fang

AU - De Yang, Yang

AU - Raben, Nina

AU - Nagaraju, Kanneboyina

AU - Rosen, Antony

AU - Casciola Rosen, Livia A

AU - Härtlein, Michael

AU - Kron, Michael

AU - Yang, David

AU - Yiadom, Kwabena

AU - Dwivedi, Sunita

AU - Plotz, Paul H.

AU - Oppenheim, Joost J.

PY - 2002/9/16

Y1 - 2002/9/16

N2 - Autoantibodies to histidyl-tRNA synthetase (HisRS) or to alanyl-, asparaginyl-, glycyl-, isoleucyl-, or threonyl-tRNA synthetase occur in ∼25% of patients with polymyositis or dermatomyositis. We tested the ability of several aminoacyl-tRNA synthetases to induce leukocyte migration. HisRS induced CD4 + and CD8 + lymphocytes, interleukin (IL)-2-activated monocytes, and immature dendritic cells (iDCs) to migrate, but not neutrophils, mature DCs, or unstimulated monocytes. An NH 2-terminal domain, 1-48 HisRS, was chemotactic for lymphocytes and activated monocytes, whereas a deletion mutant, HisRS-M, was inactive. HisRS selectively activated CC chemokine receptor (CCR)5-transfected HEK-293 cells, inducing migration by interacting with extracellular domain three. Furthermore, monoclonal anti-CCR5 blocked HisRS-induced chemotaxis and conversely, HisRS blocked anti-CCR5 binding. Asparaginyl-tRNA synthetase induced migration of lymphocytes, activated monocytes, iDCs, and CCR3-transfected HEK-293 cells. Seryl-tRNA synthetase induced migration of CCR3-transfected cells but not iDCs. Non-autoantigenic aspartyl-tRNA and lysyl-tRNA synthetases were not chemotactic. Thus, autoantigenic aminoacyl-tRNA synthetases, perhaps liberated from damaged muscle cells, may perpetuate the development of myositis by recruiting mononuclear cells that induce innate and adaptive immune responses. Therefore, the selection of a self-molecule as a target for an autoantibody response may be a consequence of the proinflammatory properties of the molecule itself.

AB - Autoantibodies to histidyl-tRNA synthetase (HisRS) or to alanyl-, asparaginyl-, glycyl-, isoleucyl-, or threonyl-tRNA synthetase occur in ∼25% of patients with polymyositis or dermatomyositis. We tested the ability of several aminoacyl-tRNA synthetases to induce leukocyte migration. HisRS induced CD4 + and CD8 + lymphocytes, interleukin (IL)-2-activated monocytes, and immature dendritic cells (iDCs) to migrate, but not neutrophils, mature DCs, or unstimulated monocytes. An NH 2-terminal domain, 1-48 HisRS, was chemotactic for lymphocytes and activated monocytes, whereas a deletion mutant, HisRS-M, was inactive. HisRS selectively activated CC chemokine receptor (CCR)5-transfected HEK-293 cells, inducing migration by interacting with extracellular domain three. Furthermore, monoclonal anti-CCR5 blocked HisRS-induced chemotaxis and conversely, HisRS blocked anti-CCR5 binding. Asparaginyl-tRNA synthetase induced migration of lymphocytes, activated monocytes, iDCs, and CCR3-transfected HEK-293 cells. Seryl-tRNA synthetase induced migration of CCR3-transfected cells but not iDCs. Non-autoantigenic aspartyl-tRNA and lysyl-tRNA synthetases were not chemotactic. Thus, autoantigenic aminoacyl-tRNA synthetases, perhaps liberated from damaged muscle cells, may perpetuate the development of myositis by recruiting mononuclear cells that induce innate and adaptive immune responses. Therefore, the selection of a self-molecule as a target for an autoantibody response may be a consequence of the proinflammatory properties of the molecule itself.

KW - Aminoacyl-tRNA synthetase

KW - Autoantibody

KW - Autoimmunity

KW - Chemokine receptor

KW - Myopathy

UR - http://www.scopus.com/inward/record.url?scp=0037120002&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037120002&partnerID=8YFLogxK

U2 - 10.1084/jem.20020186

DO - 10.1084/jem.20020186

M3 - Article

VL - 196

SP - 781

EP - 791

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 6

ER -