CCL11 increases the proportion of CD4+CD25+Foxp3+ Treg cells and the production of IL‑2 and TGF‑β by CD4+ T�cells via the STAT5 signaling pathway

Autor: Rong Wang, Keliang Huang
Rok vydání: 2020
Předmět:
CD4-Positive T-Lymphocytes
0301 basic medicine
Cancer Research
Chemokine
T-Lymphocytes
Regulatory
Biochemistry
Immune tolerance
Mice
0302 clinical medicine
STAT5 Transcription Factor
IL-2 receptor
STAT5
CCL11
biology
Chemistry
Interleukin
FOXP3
hemic and immune systems
Articles
Middle Aged
respiratory system
CD4+CD25+forkhead box P3+ regulatory T cell
Oncology
030220 oncology & carcinogenesis
CD4 Antigens
Molecular Medicine
Female
Antibody
Signal Transduction
Adult
Chemokine CCL11
Adolescent
Transplantation
Heterologous
Mice
Nude
Breast Neoplasms
chemical and pharmacologic phenomena
Transforming Growth Factor beta1
Young Adult
03 medical and health sciences
breast cancer
Immune system
Genetics
Animals
Humans
Molecular Biology
Aged
Interleukin-2 Receptor alpha Subunit
C-C motif chemokine ligand 11
Molecular biology
030104 developmental biology
Leukocytes
Mononuclear
biology.protein
Interleukin-2
Zdroj: Molecular Medicine Reports
ISSN: 1791-3004
1791-2997
Popis: CD4+ regulatory T (Treg) cells are associated with immune tolerance and antitumor immunosuppression. The aim of the present study was to investigate the role and molecular mechanism of C‑C motif chemokine ligand 11 (CCL11) in the regulation of Treg cells from patients with breast cancer (BC) and healthy individuals in vitro, and from tumor‑bearing mice in vivo. CD4+ T cells isolated from patients with BC or healthy individuals were incubated with anti‑CCL11 neutralizing antibodies or recombinant human CCL11 protein, in the presence or absence of a STAT5 inhibitor. The serum CCL11 level and proportion of Treg cells characterized as CD4+CD25+forkhead box P3+ (Foxp3) among the CD4+ T cells in patients with BC and healthy individuals were analyzed by ELISA and flow cytometry, respectively. CCL11, C‑C motif chemokine receptor 3 (CCR3), Foxp3, phosphorylated‑STAT5 and STAT5 expression levels were determined by western blotting. The serum CCL11 level and the proportion of CD4+CD25+Foxp3+ Treg cells were significantly increased in patients with BC compared with healthy individuals. CCL11 blockade reduced the proportion of CD4+CD25+Foxp3+ Treg cells, the expression of CCR3 and Foxp3, and the level of STAT5 activation in tumor‑associated CD4+ T cells, in a dose‑dependent manner. CCL11 blockade also reduced the proportion of CD4+CD25+Foxp3+ Treg cells and the serum levels of interleukin (IL)‑2 and transforming growth factor (TGF)‑β1 in tumor‑bearing mice. The recombinant human CCL11 protein increased the proportion of CD4+CD25+Foxp3+ Treg cells, the expression of CCR3 and Foxp3, and the release of IL‑2 and TGF‑β1 in non‑tumor‑associated CD4+ T cells via the STAT5 signaling pathway. The results of the present study may aid in identifying therapeutics that could further modulate the immune system during BC.
Databáze: OpenAIRE
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