Regulated expression of gp130 and IL-6 receptor alpha chain in T cell maturation and activation.
Abstract
The functional receptor for the inflammatory cytokine IL-6 is composed of the ligand binding IL-6 receptor alpha chain (IL-6R alpha) and the signal transducing chain gp130, which is a shared component of multiple cytokine receptors. We analyzed the surface expression of gp130 and IL-6R alpha in thymocytes and peripheral T cells. While all thymocytes expressed gp130 throughout thymic maturation, they gained expression of IL-6R alpha at the CD4 or CD8 single-positive stage. Approximately 10-30% of the CD4-CD8+ and 40-50% of the CD4+CD8- thymocytes expressed IL-6R alpha. Within the CD4+CD8- population, the IL-6R alpha- subpopulation was cortisone sensitive, appeared immature according to the cell surface markers expressed and failed to proliferate after TCR cross-linking. Peripheral T cells were predominantly gp130+ and IL-6R alpha+, but down-regulated gp130 and IL-6R alpha expression upon TCR engagement in vitro and in vivo. Peripheral gp130low/-IL-6R alphalow/- T cells expressed surface markers characteristic of memory T cells. We show that gp130 and IL-6R alpha are expressed in a regulated manner in T cells, depending on the developmental and functional stage.
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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 Betz and Muller, 1998
Cites
Impaired immune and acute-phase responses in interleukin-6-deficient mice
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“Transmitting editor: A. Radbruch Received 7 April 1998, accepted 28 April 1998 cell activity ( 6 ) and T cell-dependent antibody responses (6,7) are impaired, and infections with various pathogens cannot be controlled efficiently, suggesting that IL-6-mediated signals are involved in T cell function in vivo.”
BackgroundMethodInfluentialInterleukin (IL)-6 directs the differentiation of IL-4-producing CD4+ T cells
Rincón, M., Anguita, J., Nakamura, T., Fikrig, E., & Flavell, R. A. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.3.461 · Cited by 810 · see citing works
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Fraietta, J. A., Lacey, S. F., Orlando, E. J., Pruteanu-Malinici, I., Gohil, M., Lundh, S., Boesteanu, A. C., Wang, Y., O’Connor, R. S., Hwang, W.-T., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0010-1 · Cited by 1,785 · see citing works
Glioblastoma-targeted CD4+ CAR T cells mediate superior antitumor activity
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“Collectively, these data show that both WT and Il6ra−/− CD4+ T cells are responsive to trans-signaling ex vivo, but this is limited by diminished gp130 expression, consistent with activation-induced down-regulation of gp130 in CD4+ T cells (53, 55, 56).”
BackgroundMolecular basis of the cell specificity of cytokine action
Ishihara, K., & Hirano, T. (2002) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/s0167-4889(02)00321-x · Cited by 122 · see citing works
CDK8 fine-tunes IL-6 transcriptional activities by limiting STAT3 resident time at the gene loci
Martinez-Fabregas, J., Wang, L., Pohler, E., Cozzani, A., Kazemian, M., Mitra, S., & Moraga, I. (2020) · doi:10.1101/2020.03.19.998351 · Cited by 2 · see citing works
- Authors
- Betz, U.
- Affiliations
- University of Cologne (DE)
- Corresponding author
- Betz, U.
- ORCID
- Betz, U.
- Venue
- International Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1998-08-01
- Volume
- 10
- Issue
- 8
- Pages
- 1175-1184
- ISSN
- 0953-8178 (ISSN-L)
- 1460-2377
- OpenAlex
- W2144880576
- Cited by
- 70
- References
- 3
- Citations by year
- 2023: 1 · 2022: 1 · 2021: 4 · 2020: 4 · 2019: 7 · 2018: 5 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 2 · 2012: 6
- FWCI
- 0.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Immunology (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- 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
- gp130, IL-6 receptor, T cell development, thymocytes, T cell activation, memory T cells
- MeSH terms
- Animals, Cell Division, Cells, Cultured, Cortisone, Cross-Linking Reagents, Flow Cytometry, Immunologic Memory, Lymphocyte Activation, Membrane Glycoproteins, Mice, Inbred C57BL, Mice, Transgenic, Receptors, Antigen, T-Cell, Spleen, T-Lymphocytes, Tetradecanoylphorbol Acetate, Thymus Gland, Down-Regulation, Antigens, CD, Interleukin-6, Models, Immunological, Receptors, Interleukin-6, Cytokine Receptor gp130, Mice
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