Age-Related Variation in Sympathetic Nerve Distribution in the Human Spleen.

Autor:	Cleypool CGJ; Division of Surgical Specialties, Department of Anatomy, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands., Brinkman DJ; Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands.; Department of Surgery, Catharina Hospital, Eindhoven, Netherlands., Mackaaij C; Division of Surgical Specialties, Department of Anatomy, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands., Nikkels PGJ; Division of Laboratories, Pharmacy, Biomedical Genetics and Pathology, Department of Pathology, University Medical Center Utrecht, Utrecht, Netherlands., Nolte MA; Department of Molecular and Cellular Hemostasis, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands., Luyer MD; Department of Surgery, Catharina Hospital, Eindhoven, Netherlands., de Jonge WJ; Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands.; Department of Surgery, University Hospital Bonn, Bonn, Germany., Bleys RLAW; Division of Surgical Specialties, Department of Anatomy, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
Jazyk:	angličtina
Zdroj:	Frontiers in neuroscience [Front Neurosci] 2021 Oct 14; Vol. 15, pp. 726825. Date of Electronic Publication: 2021 Oct 14 (Print Publication: 2021).
DOI:	10.3389/fnins.2021.726825
Abstrakt:	Introduction: The cholinergic anti-inflammatory pathway (CAIP) has been proposed as an efferent neural pathway dampening the systemic inflammatory response via the spleen. The CAIP activates the splenic neural plexus and a subsequent series of intrasplenic events, which at least require a close association between sympathetic nerves and T cells. Knowledge on this pathway has mostly been derived from rodent studies and only scarce information is available on the innervation of the human spleen. This study aimed to investigate the sympathetic innervation of different structures of the human spleen, the topographical association of nerves with T cells and age-related variations in nerve distribution. Materials and Methods: Spleen samples were retrieved from a diagnostic archive and were allocated to three age groups; neonates, 10-25 and 25-70 years of age. Sympathetic nerves and T cells were identified by immunohistochemistry for tyrosine hydroxylase (TH) and the membrane marker CD3, respectively. The overall presence of sympathetic nerves and T cells was semi-automatically quantified and expressed as total area percentage. A predefined scoring system was used to analyze the distribution of nerves within different splenic structures. Results: Sympathetic nerves were observed in all spleens and their number appeared to slightly increase from birth to adulthood and to decrease afterward. Irrespective to age, more than halve of the periarteriolar lymphatic sheaths (PALSs) contained sympathetic nerves in close association with T cells. Furthermore, discrete sympathetic nerves were observed in the capsule, trabeculae and red pulp and comparable to the total amount of sympathetic nerves, showed a tendency to decrease with age. No correlation was found between the number of T cells and sympathetic nerves. Conclusion: The presence of discrete sympathetic nerves in the splenic parenchyma, capsule and trabecular of human spleens could suggest a role in functions other than vasoregulation. In the PALS, sympathetic nerves were observed to be in proximity to T cells and is suggestive for the existence of the CAIP in humans. Since sympathetic nerve distribution shows interspecies and age-related variation, and our general understanding of the relative and spatial contribution of splenic innervation in immune regulation is incomplete, it remains difficult to estimate the anti-inflammatory potential of targeting splenic nerves in patients. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Cleypool, Brinkman, Mackaaij, Nikkels, Nolte, Luyer, de Jonge and Bleys.)
Databáze:	MEDLINE
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