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Rapid and Robust Analysis of Cellular and Molecular Polarization Induced by Chemokine Signaling
Published on: December 12, 2014
Evaluation of Atypical Chemokine Receptor Expression in T Cell Subsets
Messias Oliveira Pacheco1, Fernanda Agostini Rocha1, Thiago Pinheiro Arrais Aloia1
1Hospital Israelita Albert Einstein, Rua Comendador Elias Jafet, São Paulo 05652-000, Brazil.
Abstract:
Chemokines are molecules that pertain to a family of small cytokines and can generate cell chemotaxis through the interaction with their receptors. Chemokines can trigger signaling via conventional G-protein-coupled receptors or through atypical chemokine receptors. Currently, four atypical chemokine receptors have been are described (ACKR1, ACKR2, ACKR3 and ACKR4). ACKRs are expressed in various cells and tissues, including T lymphocytes. These receptors' main function is related to the internalization and degradation of chemokines, as well as to the inflammation control. However, the expression of these receptors in human T lymphocytes is unclear in the literature. The objective of this study was to evaluate the expression of ACKRs in different subpopulations of T lymphocytes. For this, peripheral blood from healthy donors was used to analyze the expression of ACKR2, ACKR3 and ACKR4 by immunophenotyping CD4, CD8 T lymphocytes and, in their subsets, naive, transition and memory. Results obtained in this study demonstrated that ACKR2, ACKR3 and ACKR4 receptors were expressed by T lymphocytes subsets in different proportions. These receptors are highly expressed in the cytoplasmic milieu of all subsets of T lymphocytes, therefore suggesting that their expression in plasma membrane is regulated after transcription, and it must be dependent on a stimulus, which was not identified in our study. Thus, regarding ACKRs function as scavenger receptors, at least for the ACKR3, this function does not impair the chemotaxis exert for their ligand compared to the typical counterpart receptor.
Insights
Atypical chemokine receptors (ACKRs) are expressed in T lymphocyte subsets, primarily intracellularly. Their surface expression and role in inflammation and chemotaxis require further investigation.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Chemokines, small cytokines, regulate cell movement (chemotaxis) via receptors.
- Atypical chemokine receptors (ACKRs) internalize and degrade chemokines, influencing inflammation.
- The expression of ACKRs in human T lymphocytes remains poorly understood.
Purpose of the Study:
- To investigate the expression of atypical chemokine receptors (ACKR2, ACKR3, ACKR4) in human T lymphocyte subpopulations.
- To determine if ACKR expression differs across naive, transitional, and memory T cells.
Main Methods:
- Peripheral blood from healthy donors was analyzed.
- Immunophenotyping was used to detect ACKR2, ACKR3, and ACKR4 expression.
- Expression was assessed in CD4+, CD8+ T lymphocytes and their naive, transitional, and memory subsets.
Main Results:
- ACKR2, ACKR3, and ACKR4 were expressed by T lymphocyte subsets in varying proportions.
- These receptors showed high expression within the cytoplasm of all T lymphocyte subsets.
- Intracellular localization suggests regulated plasma membrane expression dependent on unknown stimuli.
Conclusions:
- T lymphocyte subsets express ACKR2, ACKR3, and ACKR4, predominantly intracellularly.
- Surface expression appears regulated post-transcriptionally, likely stimulus-dependent.
- ACKR3's scavenger function may not impede ligand chemotaxis via typical receptors.

