Loss of CD4+ T Cell IL-6R Expression during Inflammation Underlines a Role for IL-6 Trans Signaling in the Local Maintenance of Th17 Cells
Abstract
IL-6 responses are classically orchestrated via a membrane-bound IL-6R (CD126) alpha subunit (classical IL-6R signaling) or through a soluble form of this cognate receptor (IL-6 trans signaling). Appraisal of IL-6R expression on human and mouse T cells emphasized that IL-6R expression is closely linked with that of CCR7 and CD62L. In this regard, infiltrating effector T cells from clinical and experimental peritonitis episodes lose IL-6R expression, and anti-CD3/CD28 Ab costimulation of peripheral T cells in vitro leads to a downregulation in IL-6R expression. Consequently, IL-6 signaling through membrane-bound IL-6R seems to be limited to naive or central memory T cell populations. Loss of IL-6R expression by activated T cells further suggests that these effector cells might still retain IL-6 responsiveness via IL-6 trans signaling. Using IL-6R-deficient mice and recombinant tools that modulate the capacity of IL-6 to signal via its soluble receptor, we report that local control of IL-6 trans signaling regulates the effector characteristics of the T cell infiltrate and promotes the maintenance of IL-17A-secreting CD4(+) T cells. Therefore, we concluded that classical IL-6R signaling in naive or central memory CD4(+) T cells is required to steer their effector characteristics, whereas local regulation of soluble IL-6R activity might serve to maintain the cytokine profile of the Th cell infiltrate. Therefore, the activation status of a T cell population is linked with an alter…
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IL-6 receptor expression varies significantly among different T cell populations and environmental contexts.
“IL-6 receptor expression varies significantly among different T cell populations and environmental contexts”
From CDK8 fine-tunes IL-6 transcriptional activities by limiting STAT3 resident time at the gene loci (2020) · cites this paper as Jones et al., 2010
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CDK8 fine-tunes IL-6 transcriptional activities by limiting STAT3 resident time at the gene loci
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- Authors
- Jones, G. W., McLoughlin, R. M., Hammond, V. J., Parker, C. R., Williams, J. D., Malhotra, R., Scheller, J., Williams, A. S., Rose-John, S., Topley, N., & Jones, S. A.
- Affiliations
- Department of Infection, Immunity and Biochemistry
- Department of Nephrology
- Cardiff University (GB)
- GlaxoSmithKline (United Kingdom) (GB)
- Brigham and Women's Hospital (US)
- Christian-Albrechts-Universität zu Kiel (DE)
- Department of Medicine, Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School , Boston, MA 02115
- Corresponding author
- Topley, Nicholas
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-01-18
- Volume
- 184
- Issue
- 4
- Pages
- 2130-2139
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2148793188
- Cited by
- 189
- References
- 7
- Citations by year
- 2026: 10 · 2025: 6 · 2024: 7 · 2023: 13 · 2022: 13 · 2021: 12 · 2020: 9 · 2019: 16 · 2018: 14 · 2017: 13 · 2016: 5 · 2015: 9 · 2014: 15 · 2013: 11 · 2012: 14
- FWCI
- 7.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Explore Bristol Research (publishedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- IL-6 trans-signaling, soluble IL-6 receptor, CD4+ T cells, Th17 cells, IL-17A, peritonitis, effector T cells, central memory T cells, naive T cells, IL-6 receptor, T cell activation, T cell costimulation, CCR7, L-selectin
- MeSH terms
- Animals, Cell Movement, Cells, Cultured, Female, T-Lymphocytes, Helper-Inducer, Humans, Lymphocyte Activation, Male, Mice, Inbred C57BL, Peritonitis, Staphylococcal Infections, Signal Transduction, CD4-Positive T-Lymphocytes, Down-Regulation, Interleukin-6, Immunophenotyping, Cytokines, Mice, Knockout, Inflammation Mediators, Receptors, Interleukin-6, Interleukin-17, Mice
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