γδT-cell function in sepsis is modulated by C5a receptor signalling
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Summary: We previously showed that γδT cells are involved in the pathogenesis of sepsis, but, the underlying mechanisms remained unclear. The present study demonstrates, for the first time, that γδT cells express the complement C5a receptor (C5aR, CD88) and that CD88 expression in γδT cells was up‐regulated in mice following sepsis both at protein and mRNA levels. Complement C5a itself contributed to the regulation of C5aR expression on γδT cells, as (i) neutralization of C5a in vivo prevented the expression of C5aR on γδT cells in septic mice and (ii) incubation of mouse spleen cells or purified γδT cells with recombinant C5a in vitro increased CD88 expression by γδT cells at both protein and mRNA levels. C5a receptor on γδT cells also mediates increased interleukin‐17 (IL‐17) expression as incubation of mouse spleen cells or purified γδT cells with recombinant C5a promotes the IL‐17 expression by γδT cells. Ligation of the C5aR on γδT cells activated the phosphoinositide 3‐kinase (PI3K)/Akt signalling pathway, which enhances CD88 expression and promotes IL‐17 secretion. These results demonstrate that C5a acts directly on the C5aR expressed on γδT cells, resulting in cell activation, and subsequently enhances their capacity for IL‐17 production. The up‐regulation of the PI3K/Akt pathway following C5a stimulation contributes to up‐regulation of γδT‐cell function.
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C5a is essential for the development and regulation of T-cell immunity.
“it is also essential for the development and regulation of T-cell immunity [187,188,189,190,191,192,193].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [190]
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Cites
The phosphoinositide 3-kinase pathway
Cantley, L. C. (2002) · Science · doi:10.1126/science.296.5573.1655 · Cited by 5,621 · see citing works
Baeuerle, P. A., & Baltimore, D. (1996) · Cell · doi:10.1016/s0092-8674(00)81318-5 · Cited by 3,002 · see citing works
G-protein-coupled receptors and signaling networks: emerging paradigms
Marinissen, M. J., & Gutkind, J. S. (2001) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)01678-3 · Cited by 1,049 · see citing works
The complement system in regulation of adaptive immunity
Carroll, M. C. (2004) · Nature Immunology · doi:10.1038/ni1113 · Cited by 1,035 · see citing works
ROLE OF C5A IN INFLAMMATORY RESPONSES
Guo, R., & Ward, P. A. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115835 · Cited by 1,026 · see citing works
Advances in protein kinase B signalling: AKTion on multiple fronts
Brazil, D. P., Yang, Z., & Hemmings, B. A. (2004) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2004.03.006 · Cited by 826 · see citing works
γδ T cells: functional plasticity and heterogeneity
Carding, S. R., & Egan, P. J. (2002) · Nature Reviews Immunology · doi:10.1038/nri797 · Cited by 814 · see citing works
Guha, M., & Mackman, N. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203298200 · Cited by 799 · see citing works
Lockhart, E., Green, A. M., & Flynn, J. L. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.7.4662 · Cited by 767 · see citing works
PI3K and negative regulation of TLR signaling
Fukao, T., & Koyasu, S. (2003) · Trends in Immunology · doi:10.1016/s1471-4906(03)00139-x · Cited by 612 · see citing works
Strainic, M. G., Liu, J., Huang, D., An, F., Lalli, P. N., Muqim, N., Shapiro, V. S., Dubyak, G. R., Heeger, P. S., & Medof, M. E. (2008) · Immunity · doi:10.1016/j.immuni.2008.02.001 · Cited by 580 · see citing works
Functional roles for C5a receptors in sepsis
Rittirsch, D., Flierl, M. A., Nadeau, B. A., Day, D. E., Huber-Lang, M. S., Mackay, C. R., Zetoune, F. S., Gerard, N. P., Cianflone, K., Köhl, J., et al. (2008) · Nature Medicine · doi:10.1038/nm1753 · Cited by 386 · see citing works
Ollivier, V., Parry, G. C., Cobb, R. R., de Prost, D., & Mackman, N. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.34.20828 · Cited by 333 · see citing works
γδ T cells: an important source of IL-17
Roark, C. L., Simonian, P. L., Fontenot, A. P., Born, W. K., & O’Brien, R. L. (2008) · Current Opinion in Immunology · doi:10.1016/j.coi.2008.03.006 · Cited by 325 · see citing works
Köpf, M., Abel, B., Gallimore, A., Carroll, M. C., & Bachmann, M. F. (2002) · Nature Medicine · doi:10.1038/nm0402-373 · Cited by 309 · see citing works
Exacerbation of Collagen-Induced Arthritis by Oligoclonal, IL-17-Producing γδ T Cells
Roark, C. L., French, J. D., Taylor, M. A., Bendele, A. M., Born, W. K., & O’Brien, R. L. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.8.5576 · Cited by 300 · see citing works
Lalli, P. N., Strainic, M. G., Yang, M., Lin, F., Medof, M. E., & Heeger, P. S. (2008) · Blood · doi:10.1182/blood-2008-04-151068 · Cited by 271 · see citing works
Inhibition of protein kinase B/Akt
Hill, M. M. C., & Hemmings, B. A. (2002) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(02)00193-6 · Cited by 246 · see citing works
The role of complement in inflammation and adaptive immunity
Barrington, R. A., Zhang, M., Fischer, M. B., & Carroll, M. C. (2001) · Immunological Reviews · doi:10.1034/j.1600-065x.2001.1800101.x · Cited by 231 · see citing works
Human T Cells Express the C5a Receptor and Are Chemoattracted to C5a
Nataf, S., Davoust, N., Ames, R. S., & Barnum, S. R. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.7.4018 · Cited by 215 · see citing works
Phosphoinositide 3-kinase in immunological systems
Fruman, D. A., & Cantley, L. C. (2002) · Seminars in Immunology · doi:10.1006/smim.2001.0337 · Cited by 204 · see citing works
Adverse functions of IL‐17A in experimental sepsis
Flierl, M. A., Rittirsch, D., Gao, H., Hoesel, L. M., Nadeau, B. A., Day, D. E., Zetoune, F. S., Sarma, J. V., Huber-Lang, M. S., Ferrara, J. L. M., et al. (2008) · The FASEB Journal · doi:10.1096/fj.07-105221 · Cited by 201 · see citing works
Increased C5a receptor expression in sepsis
Riedemann, N. C., Guo, R., Neff, T. A., Laudes, I. J., Keller, K. A., Sarma, V. J., Markiewski, M. M., Mastellos, D. C., Strey, C. W., Pierson, C. L., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15409 · Cited by 190 · see citing works
The Role of Complement in Danger Sensing and Transmission
Köhl, J. (2006) · Immunologic Research · doi:10.1385/ir:34:2:157 · Cited by 172 · see citing works
Complement and Toll-like receptors: Key regulators of adaptive immune responses
Hawlisch, H., & Köhl, J. (2005) · Molecular Immunology · doi:10.1016/j.molimm.2005.06.028 · Cited by 167 · see citing works
Increased C5a receptor expression in sepsis
Riedemann, N. C., Guo, R., Neff, T. A., Laudes, I. J., Keller, K. A., Sarma, V. J., Markiewski, M. M., Mastellos, D. C., Strey, C. W., Pierson, C. L., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215409 · Cited by 157 · see citing works
Protective effects of anti-C5a in sepsis-induced thymocyte apoptosis
Guo, R., Huber-Lang, M. S., Wang, X., Sarma, V. J., Padgaonkar, V. A., Craig, R. A., Riedemann, N. C., McClintock, S. D., Hlaing, T., Shi, M. M., et al. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10793 · Cited by 152 · see citing works
An essential role for complement C5a in the pathogenesis of septic cardiac dysfunction
Niederbichler, A. D., Hoesel, L. M., Westfall, M. V., Gao, H., Ipaktchi, K. R., Sun, L., Zetoune, F. S., Su, G. L., Arbabi, S., Sarma, J. V., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20051207 · Cited by 147 · see citing works
Akt Decreases Lymphocyte Apoptosis and Improves Survival in Sepsis
Bommhardt, U., Chang, K. C., Swanson, P. E., Wagner, T. H., Tinsley, K. W., Karl, I. E., & Hotchkiss, R. S. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.12.7583 · Cited by 131 · see citing works
Dendritic cell function in allostimulation is modulated by C5aR signaling
Peng, Q., Li, K., Wang, N., Li, Q., Asgari, E., Lu, B., Woodruff, T. M., Sacks, S. H., & Zhou, W. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0804186 · Cited by 116 · see citing works
cAMP-elevating agents suppress dendritic cell function
Kambayashi, T., Wallin, R. P. A., & Ljunggren, H. (2001) · Journal of Leukocyte Biology · doi:10.1189/jlb.70.6.903 · Cited by 109 · see citing works
Complement C5a Receptor Is Essential for the Optimal Generation of Antiviral CD8+ T Cell Responses
Kim, A. H. J., Dimitriou, I. D., Holland, M. C., Mastellos, D. C., Mueller, Y. M., Altman, J. D., Lambris, J. D., & Katsikis, P. D. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.4.2524 · Cited by 105 · see citing works
Cheng, L., Cui, Y. R., Shao, H., Han, G., Zhu, L., Huang, Y., O’Brien, R. L., Born, W. K., Kaplan, H. J., & Sun, D. (2008) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2008.06.007 · Cited by 89 · see citing works
Self-citationTwo different transduction pathways are activated by C3a and C5a anaphylatoxins on astrocytes
Sayah, S., Jauneau, A.-C., Patte‐Mensah, C., Tonon, M., Vaudry, H., & Fontaine, M. (2003) · Molecular Brain Research · doi:10.1016/s0169-328x(03)00046-9 · Cited by 82 · see citing works
Kastl, S., Speidl, W. S., Kaun, C., Rega‐Kaun, G., Assadian, A., Weiss, T. W., Valent, P., Hagmüller, G. W., Maurer, G., Huber, K., et al. (2006) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2006.02046.x · Cited by 74 · see citing works
γδ T cells mitigate the organ injury and mortality of sepsis
Tschöp, J., Martignoni, A., Goetzman, H. S., Choi, L. G., Wang, Q., Noel, J. G., Ogle, C. K., Pritts, T. A., Johannigman, J. A., Lentsch, A. B., et al. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0707507 · Cited by 56 · see citing works
Yokoyama, W. M., & Colonna, M. (2008) · Current Opinion in Immunology · doi:10.1016/j.coi.2008.01.004 · Cited by 39 · see citing works
Xu, R., Wang, R., Han, G., Wang, J., Chen, G., Wang, L., Li, X., Guo, R., Shen, B., & Li, Y. (2010) · European Journal of Immunology · doi:10.1002/eji.200940015 · Cited by 38 · see citing works
Self-citationGao, Y., Rajan, A. J., Raine, C. S., & Brosnan, C. F. (2001) · Journal of Autoimmunity · doi:10.1006/jaut.2001.0547 · Cited by 30 · see citing works
Homing of transgenic gammadelta T cells into murine vaginal epithelium
Rakasz, E. G. (1998) · International Immunology · doi:10.1093/intimm/10.10.1509 · Cited by 10 · see citing works
Antiviral CD8+ T cell responses: when do they require T cell help?
Wiesel, M. (2010) · ETH Zürich Research Collection · doi:10.3929/ethz-a-006243362 · Cited by 1 · see citing works
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Hammadi, S., Tzoumas, N., Ferrara, M., Meschede, I. P., Lo, K., Harris, C., Lako, M., & Steel, D. H. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12082870 · Cited by 44 · see citing works
- Authors
- Han, G., Geng, S., Li, Y., Chen, G., Wang, R., Li, X., Ma, Y., Shen, B., & Li, Y.
- Affiliations
- Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences (CN)
- Henan University (CN)
- Corresponding author
- Han, Gencheng
- Li, Yan
- Venue
- Immunology
- Publisher
- Wiley
- Published
- 2011-04-19
- Volume
- 133
- Issue
- 3
- Pages
- 340-349
- ISSN
- 0019-2805 (ISSN-L)
- 1365-2567
- PMC
- PMC3112343
- OpenAlex
- W2142948398
- Cited by
- 32
- References
- 41
- Citations by year
- 2025: 1 · 2023: 4 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 2 · 2015: 3 · 2014: 3 · 2013: 6 · 2012: 2
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- γδ T cells, sepsis, C5a, C5a receptor, IL-17, PI3K/Akt signaling, T cell activation, complement system
- MeSH terms
- Animals, Cells, Cultured, Flow Cytometry, Immunologic Factors, Male, Mice, Inbred C57BL, Recombinant Proteins, T-Lymphocytes, Signal Transduction, Up-Regulation, Complement C5a, Receptors, Antigen, T-Cell, gamma-delta, Sepsis, Reverse Transcriptase Polymerase Chain Reaction, Interleukin-17, Receptor, Anaphylatoxin C5a, Mice
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