Increased frequencies of circulating CXCL10-, CXCL8- and CCL4-producing monocytes and Siglec-3-expressing myeloid dendritic cells in systemic sclerosis patients

Tiago Carvalheiro; Sara Horta; Joel A G van Roon; Mariana Santiago; Maria J. Salvador; Hélder Trindade; Timothy R D J Radstake; José A Pereira Da Silva; Artur Paiva

doi:10.1007/s00011-017-1106-7

Increased frequencies of circulating CXCL10-, CXCL8- and CCL4-producing monocytes and Siglec-3-expressing myeloid dendritic cells in systemic sclerosis patients

Tiago Carvalheiro, Sara Horta, Joel A G van Roon, Mariana Santiago, Maria J. Salvador, Hélder Trindade, Timothy R D J Radstake, José A Pereira Da Silva, Artur Paiva

Infection & Immunity

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Abstract

OBJECTIVE: To investigate the ex vivo pro-inflammatory properties of classical and non-classical monocytes as well as myeloid dendritic cells (mDCs) in systemic sclerosis (SSc) patients.

METHODS: Spontaneous production of CXCL10, CCL4, CXCL8 and IL-6 was intracellularly evaluated in classical, non-classical monocytes and Siglec-3-expressing mDCs from peripheral blood of SSc patients and healthy controls (HC) through flow cytometry. In addition, production of these cytokines was determined upon toll-like receptor (TLR) 4 plus Interferon-γ (IFN-γ) stimulation.

RESULTS: The frequency of non-classical monocytes spontaneously producing CXCL10 was increased in both limited (lcSSc) and diffuse cutaneous (dcSSC) subsets of SSc patients and CCL4 was augmented in dcSSc patients. The proportion of CCL4-producing mDCs was also elevated in dcSSc patients and the percentage of mDCS producing CXCL10 only in lcSSc patients. Upon stimulation, the frequency of non-classical monocytes expressing CXCL8 was increased in both patient groups and mDCs expressing CXCL8 only in lcSSc. Moreover, these parameters in unsupervised clustering analysis identify a subset of patients which are characterized by lung fibrosis and reduced pulmonary function.

CONCLUSIONS: These data point towards a role of activated non-classical monocytes and mDCs producing enhanced levels of proinflammatory cytokines in SSc, potentially contributing to lung fibrosis.

Original language	English
Pages (from-to)	169-177
Number of pages	9
Journal	Inflammation Research
Volume	67
Issue number	2
Early online date	10 Nov 2017
DOIs	https://doi.org/10.1007/s00011-017-1106-7
Publication status	Published - 1 Feb 2018

Keywords

Myeloid dendritic cells
Systemic sclerosis
Classical monocytes
Inflammation
Non-classical monocytes
Chemokines
Dendrites/metabolism
Humans
Middle Aged
Male
Interleukin-8/metabolism
Adult
Female
Interferons/metabolism
Pulmonary Fibrosis/metabolism
Sialic Acid Binding Ig-like Lectin 1/metabolism
Scleroderma, Systemic/metabolism
Chemokine CCL4/metabolism
Toll-Like Receptor 4/metabolism
Aged
Myeloid Cells/metabolism
Cytokines/biosynthesis
Chemokine CXCL10/metabolism
Monocytes/metabolism

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Carvalheiro, T., Horta, S., van Roon, J. A. G., Santiago, M., Salvador, M. J., Trindade, H., Radstake, T. R. D. J., Da Silva, J. A. P., & Paiva, A. (2018). Increased frequencies of circulating CXCL10-, CXCL8- and CCL4-producing monocytes and Siglec-3-expressing myeloid dendritic cells in systemic sclerosis patients. Inflammation Research, 67(2), 169-177. https://doi.org/10.1007/s00011-017-1106-7

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title = "Increased frequencies of circulating CXCL10-, CXCL8- and CCL4-producing monocytes and Siglec-3-expressing myeloid dendritic cells in systemic sclerosis patients",

abstract = "OBJECTIVE: To investigate the ex vivo pro-inflammatory properties of classical and non-classical monocytes as well as myeloid dendritic cells (mDCs) in systemic sclerosis (SSc) patients.METHODS: Spontaneous production of CXCL10, CCL4, CXCL8 and IL-6 was intracellularly evaluated in classical, non-classical monocytes and Siglec-3-expressing mDCs from peripheral blood of SSc patients and healthy controls (HC) through flow cytometry. In addition, production of these cytokines was determined upon toll-like receptor (TLR) 4 plus Interferon-γ (IFN-γ) stimulation.RESULTS: The frequency of non-classical monocytes spontaneously producing CXCL10 was increased in both limited (lcSSc) and diffuse cutaneous (dcSSC) subsets of SSc patients and CCL4 was augmented in dcSSc patients. The proportion of CCL4-producing mDCs was also elevated in dcSSc patients and the percentage of mDCS producing CXCL10 only in lcSSc patients. Upon stimulation, the frequency of non-classical monocytes expressing CXCL8 was increased in both patient groups and mDCs expressing CXCL8 only in lcSSc. Moreover, these parameters in unsupervised clustering analysis identify a subset of patients which are characterized by lung fibrosis and reduced pulmonary function.CONCLUSIONS: These data point towards a role of activated non-classical monocytes and mDCs producing enhanced levels of proinflammatory cytokines in SSc, potentially contributing to lung fibrosis.",

keywords = "Myeloid dendritic cells, Systemic sclerosis, Classical monocytes, Inflammation, Non-classical monocytes, Chemokines, Dendrites/metabolism, Humans, Middle Aged, Male, Interleukin-8/metabolism, Adult, Female, Interferons/metabolism, Pulmonary Fibrosis/metabolism, Sialic Acid Binding Ig-like Lectin 1/metabolism, Scleroderma, Systemic/metabolism, Chemokine CCL4/metabolism, Toll-Like Receptor 4/metabolism, Aged, Myeloid Cells/metabolism, Cytokines/biosynthesis, Chemokine CXCL10/metabolism, Monocytes/metabolism",

author = "Tiago Carvalheiro and Sara Horta and {van Roon}, {Joel A G} and Mariana Santiago and Salvador, {Maria J.} and H{\'e}lder Trindade and Radstake, {Timothy R D J} and {Da Silva}, {Jos{\'e} A Pereira} and Artur Paiva",

note = "Funding Information: Acknowledgements TC is supported by a Grant from the Portuguese national funding agency for science, research and technology: Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia [SFRH/BD/93526/2013]. Funding Information: TC is supported by a Grant from the Portuguese national funding agency for science, research and technology: Funda??o para a Ci?ncia e a Tecnologia [SFRH/BD/93526/2013]. The authors have declared no conflicts of interest. Publisher Copyright: {\textcopyright} 2017, The Author(s).",

year = "2018",

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doi = "10.1007/s00011-017-1106-7",

language = "English",

volume = "67",

pages = "169--177",

journal = "Inflammation Research",

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number = "2",

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Carvalheiro, T, Horta, S, van Roon, JAG, Santiago, M, Salvador, MJ, Trindade, H, Radstake, TRDJ, Da Silva, JAP & Paiva, A 2018, 'Increased frequencies of circulating CXCL10-, CXCL8- and CCL4-producing monocytes and Siglec-3-expressing myeloid dendritic cells in systemic sclerosis patients', Inflammation Research, vol. 67, no. 2, pp. 169-177. https://doi.org/10.1007/s00011-017-1106-7

Increased frequencies of circulating CXCL10-, CXCL8- and CCL4-producing monocytes and Siglec-3-expressing myeloid dendritic cells in systemic sclerosis patients. / Carvalheiro, Tiago; Horta, Sara; van Roon, Joel A G et al.
In: Inflammation Research, Vol. 67, No. 2, 01.02.2018, p. 169-177.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Increased frequencies of circulating CXCL10-, CXCL8- and CCL4-producing monocytes and Siglec-3-expressing myeloid dendritic cells in systemic sclerosis patients

AU - Carvalheiro, Tiago

AU - Horta, Sara

AU - van Roon, Joel A G

AU - Santiago, Mariana

AU - Salvador, Maria J.

AU - Trindade, Hélder

AU - Radstake, Timothy R D J

AU - Da Silva, José A Pereira

AU - Paiva, Artur

N1 - Funding Information: Acknowledgements TC is supported by a Grant from the Portuguese national funding agency for science, research and technology: Fundação para a Ciência e a Tecnologia [SFRH/BD/93526/2013]. Funding Information: TC is supported by a Grant from the Portuguese national funding agency for science, research and technology: Funda??o para a Ci?ncia e a Tecnologia [SFRH/BD/93526/2013]. The authors have declared no conflicts of interest. Publisher Copyright: © 2017, The Author(s).

PY - 2018/2/1

Y1 - 2018/2/1

N2 - OBJECTIVE: To investigate the ex vivo pro-inflammatory properties of classical and non-classical monocytes as well as myeloid dendritic cells (mDCs) in systemic sclerosis (SSc) patients.METHODS: Spontaneous production of CXCL10, CCL4, CXCL8 and IL-6 was intracellularly evaluated in classical, non-classical monocytes and Siglec-3-expressing mDCs from peripheral blood of SSc patients and healthy controls (HC) through flow cytometry. In addition, production of these cytokines was determined upon toll-like receptor (TLR) 4 plus Interferon-γ (IFN-γ) stimulation.RESULTS: The frequency of non-classical monocytes spontaneously producing CXCL10 was increased in both limited (lcSSc) and diffuse cutaneous (dcSSC) subsets of SSc patients and CCL4 was augmented in dcSSc patients. The proportion of CCL4-producing mDCs was also elevated in dcSSc patients and the percentage of mDCS producing CXCL10 only in lcSSc patients. Upon stimulation, the frequency of non-classical monocytes expressing CXCL8 was increased in both patient groups and mDCs expressing CXCL8 only in lcSSc. Moreover, these parameters in unsupervised clustering analysis identify a subset of patients which are characterized by lung fibrosis and reduced pulmonary function.CONCLUSIONS: These data point towards a role of activated non-classical monocytes and mDCs producing enhanced levels of proinflammatory cytokines in SSc, potentially contributing to lung fibrosis.

AB - OBJECTIVE: To investigate the ex vivo pro-inflammatory properties of classical and non-classical monocytes as well as myeloid dendritic cells (mDCs) in systemic sclerosis (SSc) patients.METHODS: Spontaneous production of CXCL10, CCL4, CXCL8 and IL-6 was intracellularly evaluated in classical, non-classical monocytes and Siglec-3-expressing mDCs from peripheral blood of SSc patients and healthy controls (HC) through flow cytometry. In addition, production of these cytokines was determined upon toll-like receptor (TLR) 4 plus Interferon-γ (IFN-γ) stimulation.RESULTS: The frequency of non-classical monocytes spontaneously producing CXCL10 was increased in both limited (lcSSc) and diffuse cutaneous (dcSSC) subsets of SSc patients and CCL4 was augmented in dcSSc patients. The proportion of CCL4-producing mDCs was also elevated in dcSSc patients and the percentage of mDCS producing CXCL10 only in lcSSc patients. Upon stimulation, the frequency of non-classical monocytes expressing CXCL8 was increased in both patient groups and mDCs expressing CXCL8 only in lcSSc. Moreover, these parameters in unsupervised clustering analysis identify a subset of patients which are characterized by lung fibrosis and reduced pulmonary function.CONCLUSIONS: These data point towards a role of activated non-classical monocytes and mDCs producing enhanced levels of proinflammatory cytokines in SSc, potentially contributing to lung fibrosis.

KW - Myeloid dendritic cells

KW - Systemic sclerosis

KW - Classical monocytes

KW - Inflammation

KW - Non-classical monocytes

KW - Chemokines

KW - Dendrites/metabolism

KW - Humans

KW - Middle Aged

KW - Male

KW - Interleukin-8/metabolism

KW - Adult

KW - Female

KW - Interferons/metabolism

KW - Pulmonary Fibrosis/metabolism

KW - Sialic Acid Binding Ig-like Lectin 1/metabolism

KW - Scleroderma, Systemic/metabolism

KW - Chemokine CCL4/metabolism

KW - Toll-Like Receptor 4/metabolism

KW - Aged

KW - Myeloid Cells/metabolism

KW - Cytokines/biosynthesis

KW - Chemokine CXCL10/metabolism

KW - Monocytes/metabolism

UR - http://www.scopus.com/inward/record.url?scp=85033467240&partnerID=8YFLogxK

U2 - 10.1007/s00011-017-1106-7

DO - 10.1007/s00011-017-1106-7

M3 - Article

C2 - 29127442

SN - 1023-3830

VL - 67

SP - 169

EP - 177

JO - Inflammation Research

JF - Inflammation Research

IS - 2

ER -

Increased frequencies of circulating CXCL10-, CXCL8- and CCL4-producing monocytes and Siglec-3-expressing myeloid dendritic cells in systemic sclerosis patients

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