Neutrophils Are Essential As A Source Of Il-17 In The Effector Phase Of Arthritis
Open accessAbstract
OBJECTIVE: Th17 has been shown to have a pivotal role in the development of arthritis. However, the role of IL-17 in the T cell-independent effector phase has not fully been examined. We investigated whether IL-17 is involved in the effector phase of arthritis by using K/BxN serum-induced arthritis model. METHODS: K/BxN serum was transferred into IL-17 knockout (KO) mice, SCID mice and their control mice, and arthritis was evaluated over time. In order to clarify the source of IL-17 in the effector phase, neutrophils or CD4+ T cells collected from IL-17 KO or control mice were injected into IL-17 KO recipient mice together with K/BxN serum. To examine if neutrophils secrete IL-17 upon stimulation, neutrophils were stimulated with immune complex in vitro and IL-17 in the supernatant was measured by ELISA. RESULTS: K/BxN serum-induced arthritis was much less severe in IL-17 KO mice than in WT mice. Since K/BxN serum-transferred SCID mice developed severe arthritis with high serum IL-17 concentration, we speculated neutrophils are the responsible player as an IL-17 source. When wild type (WT) but not IL-17 KO neutrophils were co-injected with K/BxN serum into IL-17 KO mice, arthritis was exacerbated, whereas co-injection of WT CD4+ T cells had no effect. In vitro, stimulation of neutrophils with immune complex caused IL-17 secretion. CONCLUSIONS: Neutrophils are essential as a source of IL-17 in the effector phase of arthritis. The trigger of secreting IL-17 from neutrophils may be immune complex.
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IL-17, produced primarily by CD4+ Th17 cells, acts to enhance chemokine production by target cells in various tissues to promote/attract monocytes and neutrophils to those tissue (especially mucosal) sites, and in combination with sICAM suggests the predominance of a Th1 phenotypic response (acute pro-inflammatory state).
“IL-17, produced primarily by CD4+ Th17 cells, acts to enhance chemokine production by target cells in various tissues to promote/attract monocytes and neutrophils to those tissue (especially mucosal) sites, and in combination with sICAM suggests the predominance of a Th1 phenotypic response (acute pro-inflammatory state) [25-30].”
From Oral neutrophils are an independent marker of the systemic inflammatory response after cardiac bypass (2014) · cites this paper as [28]
Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredIL-17 promotes endothelial activation by inducing the expression of endothelial adhesion markers (E-selectin, VCAM-1, and ICAM-1) in a p38 MAPK-dependent manner.
“IL-17 promotes endothelial activation by inducing the expression of endothelial adhesion markers (E-selectin, VCAM-1, and ICAM-1) in a p38 MAPK-dependent manner.”
From Oral neutrophils are an independent marker of the systemic inflammatory response after cardiac bypass (2014) · cites this paper as [28]
The Introduction says IL-17 can induce endothelial cells to secrete inflammatory cytokines, but does not address adhesion-marker expression. Searches for E-selectin, VCAM-1, ICAM-1, endothelial activation, and p38 MAPK found no passage supporting the claimed mechanism; our copy is not marked as truncated. (LLM, conf=0.73)
Experimental — accuracy not yet measuredThis increased expression of adhesion molecules stimulates the trans-endothelial migration of neutrophils.
“This increased expression of adhesion molecules stimulates the trans-endothelial migration of neutrophils) [25-29].”
From Oral neutrophils are an independent marker of the systemic inflammatory response after cardiac bypass (2014) · cites this paper as [28]
The Results section (“Neutrophils Can Secrete IL-17”) addresses immune-complex stimulation of neutrophils and IL-17 secretion. The Discussion mentions increased vascular permeability, but neither passage addresses increased adhesion-molecule expression or its effect on neutrophil trans-endothelial migration. Searches for those terms found no supporting passage in our copy; page numbers were unavailable. (LLM, conf=0.72)
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Cites
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
T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines
Fossiez, F., Djossou, O., Chomarat, P., Flores-Romo, L., Ait-Yahia, S., Maat, C., Pin, J. J., Garrone, P., Garcia, E., Saeland, S., et al. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.6.2593 · Cited by 1,526 · cited 2× · see citing works
“IL-17 induces fibroblasts, endothelial cells or macrophages to secrete IL6, TNFa and IL-1 [2,3,4].”
BackgroundSuppression of Immune Induction of Collagen-Induced Arthritis in IL-17-Deficient Mice
Nakae, S., Nambu, A., Sudo, K., & Iwakura, Y. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.11.6173 · Cited by 1,272 · see citing works
Self-citationHerpesvirus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor
Yao, Z., Fanslow, W. C., Seldin, M. F., Rousseau, A.-M., Painter, S. L., Comeau, M. R., Cohen, J. I., & Spriggs, M. K. (1995) · Immunity · doi:10.1016/1074-7613(95)90070-5 · Cited by 995 · see citing works
Jovanović, D., Battista, J. A. D., Pelletier, J., Jolicoeur, F. C., He, Y., Zhang, M., Mineau, F., & Martel‐Pelletier, J. (1998) · PubMed · Cited by 973 · see citing works
Organ-specific disease provoked by systemic autoimmunity.
Kouskoff, V., Korganow, A., Duchatelle, V., Degott, C., Benoist, C., & Mathis, D. (1996) · Cell · doi:10.1016/s0092-8674(00)81989-3 · Cited by 949 · see citing works
Mast Cells and Neutrophils Release IL-17 through Extracellular Trap Formation in Psoriasis
Lin, A. M., Rubin, C. J., Khandpur, R., Wang, J. Y., Riblett, M., Yalavarthi, S., Villanueva, E. C., Shah, P., Kaplan, M. J., & Bruce, A. T. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100123 · Cited by 906 · see citing works
Jovanović, D., Battista, J. A. D., Martel‐Pelletier, J., Jolicoeur, F. C., He, Y., Zhang, M., Mineau, F., & Pelletier, J. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.7.3513 · Cited by 867 · 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
Mast Cells: A Cellular Link Between Autoantibodies and Inflammatory Arthritis
Lee, D. M., Friend, D. S., Gurish, M. F., Benoist, C. O., Mathis, D. J., & Brenner, M. B. (2002) · Science · doi:10.1126/science.1073176 · Cited by 751 · see citing works
From Systemic T Cell Self-Reactivity to Organ-Specific Autoimmune Disease via Immunoglobulins
Korganow, A., Ji, H., Mangialaio, S., Duchatelle, V., Pelanda, R., Martin, T., Degott, C., Kikutani, H., Rajewsky, K., Pasquali, J., et al. (1999) · Immunity · doi:10.1016/s1074-7613(00)80045-x · Cited by 691 · see citing works
Arthritis Critically Dependent on Innate Immune System Players
Ji, H., Ohmura, K., Mahmood, U., Lee, D. M., Hofhuis, F. M., Boackle, S. A., Takahashi, K., Holers, V. M., Walport, M. J., Gerard, C. J., et al. (2002) · Immunity · doi:10.1016/s1074-7613(02)00275-3 · Cited by 687 · see citing works
Self-citationArthritis provoked by linked T and B cell recognition of a glycolytic enzyme.
Matsumoto, I., Staub, A., Benoist, C., & Mathis, D. (1999) · Science · doi:10.1126/science.286.5445.1732 · Cited by 667 · see citing works
Wipke, B. T., & Allen, P. M. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.3.1601 · Cited by 588 · see citing works
Ferretti, S., Bonneau, O., Dubois, G. R., Jones, C. E., & Trifilieff, A. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.4.2106 · Cited by 542 · see citing works
Nakae, S., Saijo, S., Horai, R., Sudo, K., Mori, S., & Iwakura, Y. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1035999100 · Cited by 490 · see citing works
Self-citationLi, L., Huang, L., Vergis, A. L., Ye, H., Bajwa, A., Narayan, V., Strieter, R. M., Rosin, D. L., & Okusa, M. D. (2009) · Journal of Clinical Investigation · doi:10.1172/jci38702 · Cited by 485 · see citing works
Cutting Edge: Mast Cells Express IL-17A in Rheumatoid Arthritis Synovium
Hueber, A. J., Asquith, D. L., Miller, A. M., Reilly, J. S., Kerr, S. C., Leipe, J., Melendez, A. J., & McInnes, I. B. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903566 · Cited by 358 · see citing works
Critical Roles for Interleukin 1 and Tumor Necrosis Factor α in Antibody-induced Arthritis
Ji, H., Pettit, A. R., Ohmura, K., Ortiz-Lopez, A., Duchatelle, V., Degott, C., Gravallese, E. M., Mathis, D. J., & Benoist, C. O. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020439 · Cited by 329 · see citing works
Self-citatioństergaard, M., Hansen, M. S., Stoltenberg, M., Gideon, P., Klarlund, M., Jensen, K. E., & Lorenzen, I. (1999) · Arthritis & Rheumatism · doi:10.1002/1529-0131(199905)42:5 · Cited by 323 · see citing works
Michel, M., Mendes‐da‐Cruz, D. A., Keller, A. C., Lochner, M., Schneider, E., Dy, M., Eberl, G., & Leite‐de‐Moraes, M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806472105 · Cited by 244 · see citing works
Ito, Y., Usui, T., Kobayashi, S., Iguchi-Hashimoto, M., Ito, H., Yoshitomi, H., Nakamura, T., Shimizu, M., Kawabata, D., Yukawa, N., et al. (2009) · Arthritis & Rheumatism · doi:10.1002/art.24687 · Cited by 160 · see citing works
Self-citationStaging the Initiation of Autoantibody-Induced Arthritis: A Critical Role for Immune Complexes
Wipke, B. T., Wang, Z., Nagengast, W. B., Reichert, D. E. C., & Allen, P. M. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.12.7694 · Cited by 146 · see citing works
Hoshino, A., Nagao, T., Nagi‐Miura, N., Ohno, N., Yasuhara, M., Yamamoto, K., Nakayama, T., & Suzuki, K. T. (2008) · Journal of Autoimmunity · doi:10.1016/j.jaut.2008.03.006 · Cited by 113 · see citing works
IL-17-producing T cells can augment autoantibody-induced arthritis
Jacobs, J. P., Wu, H.-J. J., Benoist, C. O., & Mathis, D. J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912152106 · Cited by 70 · see citing works
IL-17RA Signaling Amplifies Antibody-Induced Arthritis
Sadik, C. D., Kim, N. D., Alekseeva, E. A., & Luster, A. D. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026342 · Cited by 41 · see citing works
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Targeting interleukin-17 in chronic inflammatory disease: A clinical perspective
Zwicky, P., Unger, S., & Becher, B. (2020) · Journal of Experimental Medicine · doi:10.1084/jem.20191123 · Cited by 91 · see citing works
Wilcox, M. E., Charbonney, E., d’Empaire, P. P., Duggal, A., Pinto, R., Javid, A., Dos Santos, C., Rubenfeld, G. D., Sutherland, S., Liles, W. C., et al. (2014) · Journal of Inflammation · doi:10.1186/s12950-014-0032-5 · Cited by 17 · see citing works
“This increased expression of adhesion molecules stimulates the trans-endothelial migration of neutrophils) [25-29].”
Background
- Authors
- Katayama, M., Ohmura, K., Yukawa, N., Terao, C., Hashimoto, M., Yoshifuji, H., Kawabata, D., Fujii, T., Iwakura, Y., & Mimori, T.
- Affiliations
- Kyoto University (JP)
- Institute of Medical Science, The University of Tokyo (JP)
- Corresponding author
- Ohmura, Koichiro
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-05-06
- Volume
- 8
- Issue
- 5
- Pages
- e62231
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3646022
- OpenAlex
- W2102518833
- Cited by
- 66
- References
- 26
- Citations by year
- 2024: 2 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 3 · 2019: 8 · 2018: 5 · 2017: 6 · 2016: 15 · 2015: 6 · 2014: 7 · 2013: 2
- FWCI
- 8.20
- Type
- journal article
- Language
- en
- Update notices
- correction (2013-12-13)
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (22390201, 24659274)
- Topics
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- IL-17, neutrophils, Th17 cells, immune complexes, CD4+ T cells, autoimmunity
- MeSH terms
- Animals, Ankle Joint, Arthritis, Rheumatoid, Cells, Cultured, Mice, Inbred C57BL, Mice, Inbred ICR, Neutrophils, CD4-Positive T-Lymphocytes, Mice, SCID, Mice, Inbred NOD, Mice, Knockout, Interleukin-17
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