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Isolation and Adoptive Transfer of High Salt Treated Antigen-presenting Dendritic Cells
Published on: March 5, 2019
Distribution and maturation state of peripheral blood dendritic cells in children with primary hypertension
Izabela Kubiszewska1, Lidia Gackowska1, Łukasz Obrycki2
1Department of Immunology, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Torun, Poland.
Insights
Adolescents with primary hypertension show altered dendritic cell (DC) numbers and maturation, with changes correlating to organ damage. White coat hypertension exhibits intermediate DC phenotypes, suggesting early immune system involvement in hypertension.
Area of Science:
- Immunology
- Cardiovascular Medicine
- Pediatrics
Background:
- Dendritic cells (DCs) are crucial in immune regulation and T cell responses.
- Hypertension-mediated organ damage (HMOD) involves complex immunological pathways.
- Adolescent hypertension requires understanding of early pathophysiological mechanisms.
Purpose of the Study:
- To investigate the numbers, maturation, and activation of peripheral blood dendritic cell subsets (total DCs, myeloid DCs, plasmacytoid DCs) in adolescents with primary hypertension (PH) and white coat hypertension (WCH).
- To determine the association between DC characteristics and hypertension-mediated organ damage (HMOD) markers (cIMT, LVMI, PWV) and immune parameters in adolescents.
- To compare DC profiles across normotensive children, adolescents with WCH, and adolescents with PH.
Main Methods:
- Multicolor flow cytometry was used to quantify DC subsets (tDCs, mDCs, pDCs) and assess maturation/activation markers (CD86, CD83, HLA-DR, CD11c, CD123).
- Peripheral Th17 and T-reg cell distributions were analyzed.
- Hypertension-mediated organ damage was evaluated using carotid intima-media thickness (cIMT), left ventricular mass index (LVMI), and pulse wave velocity (PWV).
Main Results:
- Adolescents with PH exhibited reduced total and plasmacytoid DC numbers, increased myeloid DC percentages, and an elevated mDC/pDC ratio compared to normotensive and WCH groups.
- Mature myeloid and plasmacytoid DCs (CD83 high) and increased expression of DC activation markers (HLA-DR, CD86) were observed in PH.
- DC numbers and maturation markers correlated significantly with HMOD markers (PWV, LVMI, cIMT), with reduced tDCs/pDCs and increased mDCs associated with higher organ damage.
Conclusions:
- Primary hypertension in adolescents is characterized by distinct alterations in peripheral blood dendritic cell populations and maturation states.
- These dendritic cell changes are associated with hypertension-mediated organ damage, indicating a role in adolescent cardiovascular pathology.
- White coat hypertension displays an intermediate dendritic cell phenotype, suggesting potential early immune dysregulation preceding established primary hypertension.
Abstract:
Dendritic cells (DCs) play an important role in T cell alterations in primary hypertension (PH). We determined the numbers and maturation markers of peripheral blood total DCs (tDCs), myeloid cells (mDCs), and plasmacytoid cells (pDCs) and their association with hypertension-mediated organ damage (HMOD) markers and selected immune parameters in 30 adolescents with white coat hypertension (WCH), 25 adolescents with PH and a group of 35 age- and sex-matched children with normotension. Using multicolor flow cytometry, expression of maturation markers (CD86 and CD83) in tDCs (Lin1-/HLA-DR+), myeloid DCs (Lin1-/HLA-DR+/CD11c+) (mDCs), and plasmacytoid DCs (Lin1-/HLA-DR+/CD123+) (pDCs) and the distribution of peripheral Th17-bearing and T-reg cells were defined. In subjects with hypertension, carotid intima-media thickness (cIMT), left ventricular mass index (LVMI), and pulse wave velocity (PWV) were assessed. Compared with WCH and subjects with normotension, subjects with hypertension had reduced tDC and pDC numbers, an increased percentage of mDC subsets, an elevated mDC/pDC ratio, an increased population of mature mDC and pDC subsets bearing CD83 of high density, a decreased subset of CD86-bearing pDCs, and increased expression of DC activation markers (HLA-DR, CD86), as well as CD11c (mDCs) and CD123 (pDCs). PWV, LVMI, and cIMT values correlated negatively with tDCs and pDCs and positively with mDC numbers. Expression of DC maturation/activation markers (CD83, CD86, HLA-DR, CD11c, and CD123) correlated positively with PWV. Certain DC characteristics of WCH subjects resembled those of PH subjects (decreased tDC frequency and upregulation of activation marker expression). These changes correlated with HMOD. WCH subjects presented a DC phenotype that was intermediate between the normotensive and hypertensive phenotypes.
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