IL-17 Production Is Dominated by γδ T Cells rather than CD4 T Cells during Mycobacterium tuberculosis Infection
Abstract
IL-17 is a cytokine produced by T cells in response to IL-23. Recent data support a new subset of CD4 Th cells distinct from Th1 or Th2 cells that produce IL-17 and may contribute to inflammation. In this study, we demonstrate that, in naive mice, as well as during Mycobacterium tuberculosis infection, IL-17 production is primarily from gammadelta T cells and other non-CD4(+)CD8(+) cells, rather than CD4 T cells. The production of IL-17 by these cells is stimulated by IL-23 alone, and strongly induced by the cytokines, including IL-23, produced by M. tuberculosis-infected dendritic cells. IL-23 is present in the lungs early in infection and the IL-17-producing cells, such as gammadelta T cells, may represent a central innate protective response to pulmonary infection.
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Unlike mouse skin epidermal T cells that only contain DETCs, the human epidermis contains both αβ T cells and γδ T cells, and Vδ1+ γδ T cells are localized in both the epidermis and dermis.
“Unlike mouse skin epidermal T cells that only contain DETCs, the human epidermis contains both αβ T cells and γδ T cells, and Vδ1+ γδ T cells are localized in both the epidermis and dermis (40).”
From Comparing Mouse and Human Tissue-Resident γδ T Cells (2022) · cites this paper as [40]
Cites
Divergent Pro- and Antiinflammatory Roles for IL-23 and IL-12 in Joint Autoimmune Inflammation
Murphy, C. A., Langrish, C. L., Chen, Y., Blumenschein, W., McClanahan, T., Kastelein, R. A., Sedgwick, J. D., & Cua, D. J. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030896 · Cited by 1,669 · see citing works
Ferrick, D. A., Schrenzel, M. D., Mulvania, T., Hsieh, B., Ferlin, W. G., & Lepper, H. (1995) · Nature · doi:10.1038/373255a0 · Cited by 662 · see citing works
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Korn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132710 · Cited by 4,873 · see citing works
Sutton, C. E., Lalor, S. J., Sweeney, C. M., Brereton, C. F., Lavelle, E. C., & Mills, K. H. G. (2009) · Immunity · doi:10.1016/j.immuni.2009.08.001 · Cited by 1,553 · see citing works
Targeting IL-17 and TH17 cells in chronic inflammation
Miossec, P., & Kolls, J. K. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3794 · Cited by 1,414 · see citing works
Conti, H. R., Shen, F., Nayyar, N., Stocum, E., Sun, J. N., Lindemann, M. J., Ho, A. W., Hai, J. H., Yu, J. J., Jung, J. W., et al. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20081463 · Cited by 1,024 · see citing works
Interleukin-17 and its target genes: mechanisms of interleukin-17 function in disease
Onishi, R. M., & Gaffen, S. L. (2010) · Immunology · doi:10.1111/j.1365-2567.2009.03240.x · Cited by 894 · see citing works
Martin, B., Hirota, K., Cua, D. J., Stockinger, B., & Veldhoen, M. (2009) · Immunity · doi:10.1016/j.immuni.2009.06.020 · Cited by 822 · see citing works
The microbiome in infectious disease and inflammation
Honda, K., & Littman, D. R. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-074937 · Cited by 791 · see citing works
Afzali, B., Lombardi, G., Lechler, R. I., & Lord, G. M. (2007) · Clinical and Experimental Immunology · doi:10.1111/j.1365-2249.2007.03356.x · Cited by 762 · see citing works
Regulation of inflammatory responses by IL-17F
Yang, X. O., Chang, S. H., Park, H., Nurieva, R., Shah, B., Acero, L., Wang, Y.-H., Schluns, K. S., Broaddus, R. R., Zhu, Z., et al. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20071978 · Cited by 739 · see citing works
Ribot, J. C., deBarros, A., Pang, D. J., Neves, J. F., Peperzak, V., Roberts, S. J., Girardi, M., Borst, J., Hayday, A. C., Pennington, D. J., et al. (2009) · Nature Immunology · doi:10.1038/ni.1717 · Cited by 628 · see citing works
Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease
Romani, L., Fallarino, F., De Luca, A., Montagnoli, C., D’Angelo, C., Zelante, T., Vacca, C., Bistoni, F., Fioretti, M. C., Grohmann, U., et al. (2008) · Nature · doi:10.1038/nature06471 · Cited by 535 · see citing works
Griffin, G. K., Newton, G., Tarrio, M. L., Bu, D.-X., Maganto-Garcia, E., Azcutia, V., Alcaide, P., Grabie, N., Luscinskas, F. W., Croce, K. J., et al. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1200385 · Cited by 364 · see citing works
Development of interleukin-17-producing γδ T cells is restricted to a functional embryonic wave
Haas, J. D., Ravens, S., Düber, S., Sandrock, I., Oberdörfer, L., Kashani, E., Chennupati, V., Föhse, L., Naumann, R., Weiss, S., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.06.003 · Cited by 348 · see citing works
IL-1 and IL-23 Mediate Early IL-17A Production in Pulmonary Inflammation Leading to Late Fibrosis
Gasse, P., Riteau, N., Vacher, R., Michel, M.-L., Fautrel, A., di Padova, F., Fick, L., Charron, S., Lagente, V., Eberl, G., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023185 · Cited by 208 · see citing works
Intestinal Microbiota of Mice Influences Resistance to Staphylococcus aureus Pneumonia
Gauguet, S., D'Ortona, S., Ahnger-Pier, K., Duan, B., Surana, N. K., Lu, R., Cywes-Bentley, C., Gadjeva, M., Shan, Q., Priebe, G. P., et al. (2015) · Infection and Immunity · doi:10.1128/iai.00037-15 · Cited by 208 · see citing works
Cheng, M., Qian, L., Shen, G., Bian, G., Xu, T., Xu, W., Shen, G., & Hu, S. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-2462 · Cited by 182 · see citing works
Maitra, A., Shen, F., Hanel, W., Mossman, K., Tocker, J., Swart, D., & Gaffen, S. L. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611589104 · Cited by 165 · see citing works
Berry, S. P. D.-G., Dossou, C., Kashif, A., Sharifinejad, N., Azizi, G., Hamedifar, H., Sabzvari, A., & Zian, Z. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2021.108402 · Cited by 124 · see citing works
Five Layers of Receptor Signaling in γδ T-Cell Differentiation and Activation
Ribeiro, S. T., Ribot, J. C., & Silva-Santos, B. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00015 · Cited by 116 · see citing works
Avau, A., Mitera, T., Put, S., Put, K., Brisse, E., Filtjens, J., Uyttenhove, C., Van Snick, J., Liston, A., Leclercq, G., et al. (2014) · Arthritis & Rheumatology · doi:10.1002/art.38359 · Cited by 90 · see citing works
Comparing Mouse and Human Tissue-Resident γδ T Cells
Qu, G., Wang, S., Zhou, Z., Jiang, D., Liao, A., & Luo, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.891687 · Cited by 87 · see citing works
“Unlike mouse skin epidermal T cells that only contain DETCs, the human epidermis contains both ab T cells and gd T cells, and Vd1 gd T cells are localized in both the epidermis and dermis (40).”
BackgroundBuckley, K. M., Ho, E. C. H., Hibino, T., Schrankel, C. S., Schuh, N. W., Wang, G., & Rast, J. P. (2017) · eLife · doi:10.7554/elife.23481 · Cited by 77 · see citing works
Neutrophils Are Essential As A Source Of Il-17 In The Effector Phase Of Arthritis
Katayama, M., Ohmura, K., Yukawa, N., Terao, C., Hashimoto, M., Yoshifuji, H., Kawabata, D., Fujii, T., Iwakura, Y., & Mimori, T. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062231 · Cited by 66 · see citing works
Callus γδ T cells and microbe-induced intestinal Th17 cells improve fracture healing in mice
Dar, H. Y., Perrien, D. S., Pal, S., Stoica, A., Uppuganti, S., Nyman, J. S., Jones, R. M., Weitzmann, M. N., & Pacifici, R. (2023) · Journal of Clinical Investigation · doi:10.1172/jci166577 · Cited by 48 · see citing works
Tateosian, N. L., Pellegrini, J. M., Amiano, N. O., Rolandelli, A., Casco, N., Palmero, D. J., Colombo, M. I., & García, V. E. (2017) · Autophagy · doi:10.1080/15548627.2017.1320636 · Cited by 45 · see citing works
Epidermal ablation of Dlx3 is linked to IL-17-associated skin inflammation
Hwang, J., Kita, R., Kwon, H.-S., Choi, E. H., Lee, S. H., Udey, M. C., & Morasso, M. I. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019658108 · Cited by 45 · see citing works
Update on the role of Interleukin 17 in rheumatologic autoimmune diseases
Konya, C., Paz, Z., Apostolidis, S. A., & Tsokos, G. C. (2015) · Cytokine · doi:10.1016/j.cyto.2015.01.003 · Cited by 35 · see citing works
γδT-cell function in sepsis is modulated by C5a receptor signalling
Han, G., Geng, S., Li, Y., Chen, G., Wang, R., Li, X., Ma, Y., Shen, B., & Li, Y. (2011) · Immunology · doi:10.1111/j.1365-2567.2011.03445.x · Cited by 32 · see citing works
- Authors
- Lockhart, E., Green, A. M., & Flynn, J. L.
- Affiliations
- University of Pittsburgh (US)
- ORCID
- Flynn, JoAnne L
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-10-01
- Volume
- 177
- Issue
- 7
- Pages
- 4662-4669
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2152994600
- Cited by
- 767
- References
- 2
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 13 · 2023: 18 · 2022: 21 · 2021: 19 · 2020: 24 · 2019: 24 · 2018: 25 · 2017: 44 · 2016: 40 · 2015: 41 · 2014: 58 · 2013: 55 · 2012: 78
- FWCI
- 18.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (T32 CA 82084-07, T32CA082084)
- National Institute of Allergy and Infectious Diseases (AI060525, R01AI050732, AI-37859, T32AI060525)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Keywords
- IL-17, γδ T cells, CD4+ T cells, Mycobacterium tuberculosis infection, IL-23, dendritic cells, pulmonary infection, innate immunity, Th17 cells, cytokine production
- MeSH terms
- Animals, Cells, Cultured, Dendritic Cells, Female, Flow Cytometry, Interleukins, Mice, Inbred C57BL, Mycobacterium tuberculosis, Tuberculosis, CD4-Positive T-Lymphocytes, T-Lymphocyte Subsets, Receptors, Antigen, T-Cell, gamma-delta, Interleukin-17, Mice, Interleukin-23, Interleukin-23 Subunit p19
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