Corticosterone impairs dendritic cell maturation and function
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Summary: Dendritic cells (DC) play a critical role in initiating and directing adaptive immune responses against pathogens and tumours. Immature DC are thought to act as sentinels in peripheral tissues where their main function is to capture antigen at sites of infection, whereas mature DC are highly efficient at priming T‐cell‐mediated immune responses against infectious pathogens. The DC maturation process is thought to be an important step in the efficient generation of cytotoxic T lymphocytes (CTL). It is well established that many aspects of immune function, including CTL‐mediated antiviral immunity, are modulated by neuroendocrine‐derived products. Corticosterone (CORT), an adrenal hormone produced at increased concentrations during a stress response, has been shown to play a role in impaired CTL responses in stressed animals, leading to high mortality in mice normally resistant to viral infection. While direct effects of neuroendocrine mediators on CTL have been studied, little is known about their effects on DC that are critical for CTL priming. Here, we found that physiologically relevant concentrations of CORT, acting via the glucocorticoid receptor, functionally compromise DC maturation. DC exposed to CORT remained phenotypically and functionally immature after stimulation with lipopolysaccharide and were impaired for the production of interleukin (IL)‐6, IL‐12, and tumour necrosis factor‐α. These effects were biologically significant, as CORT treatment resulted in a marked reduction in the ability of DC to prime naive CD8+ T cells in vivo. These findings offer a potential mechanism underlying stress‐associated immunosuppression.
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Glucocorticoids regulate dendritic cell maturation, survival, and motility and hamper their immunogenic functions, including restricting T cell stimulation by preventing up-regulation of MHCII, B7.2, and CD40.
“In addition to regulating the maturation, survival, and motility of these antigen-presenting cells, GCs also hamper their immunogenic functions. Indeed, the end product of the HPA axis restricts the capacity of DCs to stimulate T cells by preventing the up-regulation of various co-stimulatory molecules, such as MHCII, B7.2 (CD86), and CD40 (33, 36, 37).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [36]
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The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain
Bellavance, M.-A., & Rivest, S. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00136 · Cited by 419 · see citing works
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- Authors
- Elftman, M. D., Norbury, C. C., Bonneau, R. H., & Truckenmiller, M. E.
- Affiliations
- Pennsylvania State University (US)
- Corresponding author
- Truckenmiller, Mary E.
- Venue
- Immunology
- Publisher
- Wiley
- Published
- 2007-05-10
- Volume
- 122
- Issue
- 2
- Pages
- 279-290
- ISSN
- 0019-2805 (ISSN-L)
- 1365-2567
- PMC
- PMC2265998
- OpenAlex
- W1989268226
- Cited by
- 79
- References
- 50
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 1 · 2021: 5 · 2020: 4 · 2018: 3 · 2017: 1 · 2016: 4 · 2015: 1 · 2014: 5 · 2013: 9 · 2012: 3
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pennsylvania State University
- National Institutes of Health
- National Cancer Institute (T32CA060395, 2T32 CA60395-11)
- National Institute of Allergy and Infectious Diseases (AI49719, AI065702, R01AI049719, R01AI065702)
- National Center for Research Resources (C06 RR 15428-01, C06RR015428)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- corticosterone, dendritic cell maturation, glucocorticoid receptor, CD8+ T cell priming, cytotoxic T lymphocytes, IL-12, interleukin-6, TNF-α, lipopolysaccharide, neuroendocrine-immune regulation, antiviral immunity
- MeSH terms
- Animals, Histocompatibility Antigens Class II, Antigens, Surface, Cell Differentiation, Cells, Cultured, Corticosterone, Dendritic Cells, Endocytosis, Immune Tolerance, Lipopolysaccharides, Male, Mice, Inbred C57BL, Receptors, Glucocorticoid, Up-Regulation, Cytokines, CD8-Positive T-Lymphocytes, Mice
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