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Chemokines in the systemic organization of immunity
Daniel J Campbell1, Chang H Kim, Eugene C Butcher
1Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. campbell@benaroyaresearch.org
Insights
Chemokines and their receptors guide immune cell movement, crucial for immune system organization and function. Understanding these interactions helps explain how leukocytes reach specific tissues for differentiation and activity.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Directed cellular migration is fundamental to immune system organization.
- Chemokines, their receptors, and adhesion molecules are key regulators of leukocyte trafficking.
- Specific chemokine-receptor interactions guide immune cells to appropriate tissues for development and function.
Purpose of the Study:
- To summarize the role of chemokines and their receptors in the spatial organization of the immune system.
- To explore the implications of chemokine-mediated migration for immune cell function.
- To highlight the importance of chemokine signaling in leukocyte homing and tissue localization.
Main Methods:
- Review of existing literature on chemokine and chemokine receptor function in leukocyte migration.
- Analysis of the expression patterns of chemokine receptors during different stages of leukocyte development and in mature cells.
- Examination of the roles of specific chemokine-receptor pairs (e.g., CXCL12/CXCR4, CCR7, CXCR5) in immune cell trafficking.
Main Results:
- Chemokines and receptors orchestrate the movement of leukocytes, including hematopoietic stem cells, B cells, and T cells.
- Distinct chemokine receptor expression profiles dictate cell localization during development and in the periphery.
- Mature lymphocytes use specific receptors (CCR7, CXCR4, CXCR5) to navigate secondary lymphoid tissues, while effector/memory cells exhibit unique patterns for non-lymphoid tissue access.
Conclusions:
- Chemokine and receptor signaling are critical for establishing and maintaining immune system architecture.
- Understanding these pathways provides insights into immune cell homing, tissue-specific functions, and immune responses.
- Dysregulation of chemokine-mediated migration may have implications for immune-related diseases.
Abstract:
Directed cellular migrations underlie immune system organization. Chemokines and their receptors (along with surface-adhesion molecules) are central to these migrations, targeting developing and mature leukocytes to tissues and microenvironments suitable for their differentiation and function. The chemokine CXCL12 and its receptor CXCR4 play a central role in the migration of hematopoietic stem cells, and several chemokine receptors are transiently expressed during distinct stages of B- and T-cell development. In the periphery, mature naïve B and T cells utilize the receptors CCR7, CXCR4, and CXCR5 to recirculate through specialized microenvironments within the secondary lymphoid tissues, while effector and memory lymphocytes express bewildering patterns of adhesion molecules and chemokine receptors that allow them to function within microenvironments and non-lymphoid tissues inaccessible to naïve cells. Here, we summarize the role of chemokines and their receptors in the spatial organization of the immune system and consider the implications for immune function.