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Research ArticleSystemic Lupus Erythematosus

Altered Homeostasis of Regulatory T Lymphocytes and Differential Regulation of STAT1/STAT5 in CD4+ T Lymphocytes in Childhood-onset Systemic Lupus Erythematosus

Marija Holcar, Aleš Goropevšek and Tadej Avčin
The Journal of Rheumatology April 2020, 47 (4) 557-566; DOI: https://doi.org/10.3899/jrheum.181418
Marija Holcar
From the Department of Allergology, Rheumatology and Clinical Immunology, University Children’s Hospital, University Medical Centre Ljubljana, Ljubljana; Department of Laboratory Diagnostics, University Medical Centre Maribor, Maribor; Department of Pediatrics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
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Aleš Goropevšek
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Tadej Avčin
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  • For correspondence: tadej.avcin@kclj.si
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Abstract

Objective. Childhood-onset systemic lupus erythematosus (cSLE) is usually a more severe and aggressive disease than adult-onset SLE (aSLE), but cellular and subcellular reasons for these differences are not well understood. The present study analyzed Th subsets, STAT1/STAT5 signaling response, and cytokine profiles of cSLE.

Methods. FOXP3+ regulatory (Treg) and effector Th subsets, expression and phosphorylation of STAT1/STAT5 in Th, and cytokine profiles were measured in the peripheral blood of patients with cSLE and healthy controls (HC), using flow cytometry and immunoassay on a biochip.

Results. Significant correlation between expression of the activation marker HLA-DR and decreased Th counts, an increase in the percentage of FOXP3+ Th, and a decrease in the activated Treg (aTreg) subset among them were found in cSLE. In contrast to our previous findings in aSLE, no significant differences in percentages and a significant decrease in the numbers of the naive-resting Treg (rTreg) subset compared to HC were found. The percentages of CD25− cells, possibly reflecting interleukin 2 depletion, were significantly increased in cSLE aTreg, but not in the rTreg subset. Consistent with the results of our previous studies in aSLE, increased expression of STAT1, along with significant correlation between decreased Th counts and their increased basal phosphorylation of STAT5, were also found in cSLE.

Conclusion. Our results suggest that the key difference in Treg homeostasis between cSLE and aSLE is in the rTreg subset. However, perturbed aTreg homeostasis, increased levels of STAT1 protein, and homeostatic STAT5 signaling appear to be intrinsic characteristics of the disease, present in cSLE and aSLE alike.

Key Indexing Terms:
  • SYSTEMIC LUPUS ERYTHEMATOSUS
  • CHILDHOOD ONSET
  • FLOW CYTOMETRY
  • TREG
  • EFFECTOR TH
  • TH17

Footnotes

  • This work was partially supported by the Slovenian Research Agency grant (grant number L7-8274) and the University Medical Centre Ljubljana research grant (grant number 20180093).

  • Accepted for publication June 20, 2019.
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The Journal of Rheumatology
Vol. 47, Issue 4
1 Apr 2020
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Altered Homeostasis of Regulatory T Lymphocytes and Differential Regulation of STAT1/STAT5 in CD4+ T Lymphocytes in Childhood-onset Systemic Lupus Erythematosus
Marija Holcar, Aleš Goropevšek, Tadej Avčin
The Journal of Rheumatology Apr 2020, 47 (4) 557-566; DOI: 10.3899/jrheum.181418

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Altered Homeostasis of Regulatory T Lymphocytes and Differential Regulation of STAT1/STAT5 in CD4+ T Lymphocytes in Childhood-onset Systemic Lupus Erythematosus
Marija Holcar, Aleš Goropevšek, Tadej Avčin
The Journal of Rheumatology Apr 2020, 47 (4) 557-566; DOI: 10.3899/jrheum.181418
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Keywords

SYSTEMIC LUPUS ERYTHEMATOSUS
CHILDHOOD ONSET
FLOW CYTOMETRY
TREG
EFFECTOR TH
TH17

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Keywords

  • systemic lupus erythematosus
  • CHILDHOOD ONSET
  • FLOW CYTOMETRY
  • TREG
  • EFFECTOR TH
  • TH17

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