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Cytokines and macrophages: implications for normal and abnormal renal development
1Department of Clinical Immunology, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London, WC1N 3JH, UK. catherine.cale@gosh-tr.nthames.nhs.uk
Abstract:
Work with transgenic animals and in vitro manipulation of organs in culture has highlighted an increasing number of genes that are important in the normal development of the kidney and whose disruption inhibits nephrogenesis. The phenotype seen with some agents resembles that of the congenital renal anomaly renal dysplasia, in which there appears to be an arrest of normal development. Such molecules include inflammatory cytokines, factors that have traditionally been described as intercellular messengers in the immune system. Although the mechanisms of action of cytokines in organogenesis have not yet been fully delineated, these may include alterations in normal expression patterns of adhesion molecules, modulation of extracellular matrix, influencing the levels of other cytokines and interactions with transcription factors. Furthermore, macrophages are among the first haematopoietic cells to be found in the kidney and other embryonic tissues. Their numbers and activation status are closely regulated by cytokines and evidence is accumulating that as well as scavenging cellular debris, macrophages themselves may induce cell death during organogenesis. Disruption of any of these carefully regulated and interdependent processes may cause disease.
Insights
Genes and inflammatory cytokines are crucial for kidney development (nephrogenesis). Disruptions can lead to congenital anomalies like renal dysplasia, highlighting the complex interplay of immune factors in organogenesis.
Area of Science:
- Developmental biology
- Immunology
- Renal physiology
Background:
- Gene disruption and in vitro organ culture reveal genes critical for normal kidney development (nephrogenesis).
- Certain disruptions mimic congenital renal anomalies like renal dysplasia, characterized by arrested development.
- Inflammatory cytokines, immune system messengers, are implicated in these developmental processes.
Purpose of the Study:
- To explore the role of genes and inflammatory cytokines in kidney development and nephrogenesis.
- To understand how disruptions in these processes lead to congenital renal anomalies.
- To investigate the mechanisms by which cytokines influence organogenesis.
Main Methods:
- Utilizing transgenic animal models.
- Employing in vitro organ culture techniques.
- Analyzing gene expression patterns and cellular interactions.
Main Results:
- Identified numerous genes essential for normal kidney development.
- Observed that inflammatory cytokines can disrupt nephrogenesis, leading to phenotypes resembling renal dysplasia.
- Highlighted the potential roles of cytokines in altering adhesion molecule expression, extracellular matrix, and transcription factor interactions.
- Noted the early presence and regulatory role of macrophages in embryonic kidneys, influenced by cytokines.
Conclusions:
- Cytokines and macrophages play significant roles in kidney organogenesis.
- Disruption of cytokine signaling or macrophage function can impair nephrogenesis and lead to kidney disease.
- The intricate regulation of these processes is vital for preventing congenital renal anomalies.