Introduction

Langerhans cells (LCs) are closely associated with sensory nerve fibers in the skin and express neurotransmitter receptors, enabling interaction with the peripheral nervous system. The neuropeptide Calcitonin Gene-Related Peptide (CGRP) may regulate the antigen-presenting function of LCs, providing evidence of regulatory mechanisms mediating interactions between the immune and nervous systems in the skin. However, the skin is a complex structure influenced by diverse intrinsic and extrinsic factors, which play a critical role in the body’s response to skin diseases. Hence, this study aims to evaluate the interaction between LCs and CGRP-expressing neurons in human skin with respect to age, body mass index (BMI), smoking habits, and anatomical region differences.

Methods

In this study, skin tissue samples were obtained from 60 volunteers aged 20 to 70 years. For general histological analyses, samples were stained with toluidine blue, Masson’s trichrome, and hematoxylin-eosin, while immunofluorescent evaluations included CD207, CD1a, and CGRP immunostaining.

Results

Consequently, smoking status and BMI did not cause statistically significant changes in the number of mast cells (MCs), the density of LCs, or the number of CGRP-expressing nerve endings. However, MC density increased in sun-protected older skin and sun-exposed aged (photoaged) skin compared to sun-protected young skin.

Conclusion

In photoaged skin, while LC density decreased, CGRP-expressing nerve fiber density increased. The present data are crucial for understanding neuroimmunological regulation in the skin and for elucidating how cellular coordination is both maintained and disrupted. Topical formulations of CGRP antagonists or agonists, if shown to be effective, will enhance our understanding of various skin disorders and contribute to the development of novel therapeutic approaches.

Funding Source

This project was a PhD thesis and was supported by the Scientific and Technological Research Council of Turkey (TÜBİTAK) under the grant number 1059B142100173.