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Intercellular adhesion molecule-1 and hair follicle regression
S Müller-Röver1, S Bulfone-Paus, B Handjiski
1Centre for Cutaneous Research, University of London, London, United Kingdom.
Insights
Intercellular adhesion molecule-1 (ICAM-1) plays a key role in hair follicle remodeling during the hair cycle. ICAM-1 deficiency accelerates catagen, suggesting a non-immune function in skin development.
Area of Science:
- Cutaneous biology
- Developmental biology
- Immunology
Background:
- Intercellular adhesion molecule-1 (ICAM-1) is known for its role in inflammation and immune responses.
- Its function in developmental processes, specifically hair follicle cycling (anagen and catagen), is largely unexplored.
Purpose of the Study:
- To investigate the expression patterns and functional significance of ICAM-1 during murine hair follicle development and cycling.
- To explore potential non-immunological roles of ICAM-1 in skin remodeling.
Main Methods:
- Analysis of ICAM-1 and leukocyte function-associated antigen-1 (LFA-1) expression (protein and mRNA) in murine skin during different hair cycle stages.
- Comparison of hair follicle cycling in ICAM-1-deficient mice versus wild-type controls.
Main Results:
- ICAM-1 is expressed in various skin cells, including endothelial cells, keratinocytes, and fibroblasts, with developmentally regulated and hair cycle-dependent patterns.
- Expression peaks during late anagen and catagen, particularly in outer root sheath keratinocytes, connective tissue sheath fibroblasts, and perifollicular blood vessels.
- ICAM-1-deficient mice exhibit accelerated catagen compared to wild-type mice.
Conclusions:
- ICAM-1 upregulation is crucial for normal hair follicle remodeling, extending beyond its known immunological functions.
- ICAM-1 signaling appears to play a significant, potentially non-immunological, role in cutaneous biology and development.
Abstract:
Although the intercellular adhesion molecule-1 (ICAM-1) is recognized for its pivotal role in inflammation and immune responses, its role in developmental systems, such as the cyclic growth (anagen) and regression (catagen) of the hair follicle, remains to be explored. Here we demonstrate that ICAM-1 expression in murine skin is even more widespread and more developmentally regulated than was previously believed. In addition to endothelial cells, selected epidermal and follicular keratinocyte subpopulations, as well as interfollicular fibroblasts, express ICAM-1. Murine hair follicles express ICAM-1 only late during morphogenesis. Thereafter, morphologically identical follicles markedly differ in their ICAM-1 expression patterns, which become strikingly hair cycle-dependent in both intra- and extrafollicular skin compartments. Minimal ICAM-1 and leukocyte function-associated (LFA-1) protein and mRNA expression is observed during early anagen and maximal expression during late anagen and catagen. Keratinocytes of the distal outer root sheath, fibroblasts of the perifollicular connective tissue sheath, and perifollicular blood vessels exhibit maximal ICAM-1 immunoreactivity during catagen, which corresponds to changes of LFA-1 expression on perifollicular macrophages. Finally, ICAM-1-deficient mice display significant catagen acceleration compared to wild-type controls. Therefore, ICAM-1 upregulation is not limited to pathological situations but is also important for skin and hair follicle remodeling. Collectively, this suggests a new and apparently nonimmunological function for ICAM-1-related signaling in cutaneous biology.