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The kinase TBK1 controls IgA class switching by negatively regulating noncanonical NF-κB signaling
Open accessAbstract
Immunoglobulin class switching is crucial for the generation of antibody diversity in humoral immunity and, when deregulated, also has severe pathological consequences. How the magnitude of immunoglobulin isotype switching is controlled is still poorly understood. Here we identify the kinase TBK1 as a pivotal negative regulator of class switching to the immunoglobulin A (IgA) isotype. B cell-specific ablation of TBK1 in mice resulted in uncontrolled production of IgA and the development of nephropathy-like disease signs. TBK1 negatively regulated IgA class switching by attenuating noncanonical signaling via the transcription factor NF-κB, an action that involved TBK1-mediated phosphorylation and subsequent degradation of the NF-κB-inducing kinase NIK. Our findings establish TBK1 as a pivotal negative regulator of the noncanonical NF-κB pathway and identify a unique mechanism that controls IgA production.
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“Recent studies have demonstrated critical roles for TBK1 and/or IKK ε in regulation of activity of numerous immune cell types, including T cells 21 , B cells 22,23 , dendritic cells 24 , and macrophages 25,26 .”
From Targeting TBK1 to overcome resistance to cancer immunotherapy (2023) · cites this paper as [23]
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1 retracted
RETRACTED ARTICLE: DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL
Litinskiy, M. B., Nardelli, B., Hilbert, D. M., He, B., Schaffer, A., Casali, P., & Cerutti, A. (2002) · Nature Immunology · doi:10.1038/ni829 · Cited by 1,252
RetractedThe role of pattern-recognition receptors in innate immunity: update on Toll-like receptors
Kawai, T., & Akira, S. (2010) · Nature Immunology · doi:10.1038/ni.1863 · Cited by 9,304
Shared Principles in NF-κB Signaling
Hayden, M. S., & Ghosh, S. (2008) · Cell · doi:10.1016/j.cell.2008.01.020 · Cited by 4,954
Muramatsu, M., Kinoshita, K., Fagarasan, S., Yamada, S., Shinkai, Y., & Honjo, T. (2000) · Cell · doi:10.1016/s0092-8674(00)00078-7 · Cited by 3,475
IKKε and TBK1 are essential components of the IRF3 signaling pathway
Fitzgerald, K. A., McWhirter, S. M., Faia, K. L., Rowe, D. C., Latz, E., Golenbock, D. T., Coyle, A. J., Liao, S.-M., & Maniatis, T. (2003) · Nature Immunology · doi:10.1038/ni921 · Cited by 2,680
Regulation and Function of NF-κB Transcription Factors in the Immune System
Vallabhapurapu, S., & Karin, M. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132641 · Cited by 2,635
Triggering the Interferon Antiviral Response Through an IKK-Related Pathway
Sharma, S., tenOever, B. R., Grandvaux, N., Zhou, G., Lin, R., & Hiscott, J. B. (2003) · Science · doi:10.1126/science.1081315 · Cited by 1,685
The immune geography of IgA induction and function
Macpherson, A. J., McCoy, K. D., Johansen, F.-E., & Brandtzaeg, P. (2007) · Mucosal Immunology · doi:10.1038/mi.2007.6 · Cited by 1,047
The regulation of IgA class switching
Cerutti, A. (2008) · Nature reviews. Immunology · doi:10.1038/nri2322 · Cited by 777
The noncanonical NF‐κB pathway
Sun, S. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01088.x · Cited by 752
Self-citationHemmi, H., Takeuchi, O., Sato, S., Yamamoto, M., Kaisho, T., Sanjo, H., Kawai, T., Hoshino, K., Takeda, K., & Akira, S. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040520 · Cited by 576
TACI and BAFF-R mediate isotype switching in B cells
Castigli, E., Wilson, S. A., Scott, S., Dedeoğlu, F., Xu, S., Lam, K., Bram, R. J., Jabara, H. H., & Geha, R. S. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20032000 · Cited by 544
McWhirter, S. M., Fitzgerald, K. A., Rosains, J., Rowe, D. C., Golenbock, D. T., & Maniatis, T. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2237236100 · Cited by 542
Liao, G., Zhang, M., Harhaj, E. W., & Sun, S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403286200 · Cited by 480
Self-citationTriggering the Innate Antiviral Response through IRF-3 Activation
Hiscott, J. B. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.r700002200 · Cited by 454
Alymphoplasia is caused by a point mutation in the mouse gene encoding Nf-κb-inducing kinase
Shinkura, R., Kitada, K., Matsuda, F., Tashiro, K., Ikuta, K., Suzuki, M., Kogishi, K., Serikawa, T., & Honjo, T. (1999) · Nature Genetics · doi:10.1038/8780 · Cited by 451
Interactions of Tumor Necrosis Factor (TNF) and TNF Receptor Family Members in the Mouse and Human
Bossen, C., Ingold, K., Tardivel, A., Bodmer, J.-L., Gaide, O., Hertig, S., Ambrose, C. M., Tschopp, J., & Schneider, P. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601553200 · Cited by 443
Impaired IgA class switching in APRIL-deficient mice
Castigli, E., Scott, S., Dedeoğlu, F., Bryce, P. J., Jabara, H. H., Bhan, A. K., Mizoguchi, E., & Geha, R. S. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307348101 · Cited by 432
TGF-β Receptor Controls B Cell Responsiveness and Induction of IgA In Vivo
Cazac, B. B., & Roes, J. (2000) · Immunity · doi:10.1016/s1074-7613(00)00044-3 · Cited by 430
Franzoso, G., Carlson, L. M., Poljak, L., Shores, E. W., Epstein, S. L., Leonardi, A., Grinberg, A., Tran, T., Scharton‐Kersten, T., Anver, M. R., et al. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.187.2.147 · Cited by 425
Defective Lymphotoxin-β Receptor-Induced NF-κB Transcriptional Activity in NIK-Deficient Mice
Li, Y., Wu, L., Wesche, H., Arthur, C. D., White, J. M., Goeddel, D. V., & Schreiber, R. D. (2001) · Science · doi:10.1126/science.1058453 · Cited by 408
Perry, A. K., Chow, E. K., Goodnough, J. B., Yeh, W., & Cheng, G. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040528 · Cited by 396
Caamaño, J., Rizzo, C. A., Durham, S. K., Barton, D. S., Raventós-Suárez, C., Snapper, C. M., & Bravo, R. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.187.2.185 · Cited by 395
Bonnard, M., Mirtsos, C., Suzuki, S., Graham, K., Huang, J., Ng, M., Itié, A., Wakeham, A., Shahinian, A., Henzel, W. J., et al. (2000) · The EMBO Journal · doi:10.1093/emboj/19.18.4976 · Cited by 381
Common variable immunodeficiency: a new look at an old disease
Park, M. A., Li, J. T., Hagan, J. B., Maddox, D. E., & Abraham, R. S. (2008) · The Lancet · doi:10.1016/s0140-6736(08)61199-x · Cited by 363
Multiple Functions of the IKK-Related Kinase IKKε in Interferon-Mediated Antiviral Immunity
tenOever, B. R., Ng, S., Chua, M. A., McWhirter, S. M., García‐Sastre, A., & Maniatis, T. (2007) · Science · doi:10.1126/science.1136567 · Cited by 342
Novel cross-talk within the IKK family controls innate immunity
Clark, K., Peggie, M., Plater, L., Sorcek, R. J., Young, E. R. R., Madwed, J. B., Hough, J., McIver, E. G., & Cohen, P. (2011) · Biochemical Journal · doi:10.1042/bj20101701 · Cited by 326
Mice overexpressing BAFF develop a commensal flora–dependent, IgA-associated nephropathy
McCarthy, D. D., Kujawa, J., Wilson, C. B., Papandile, A., Poreci, U., Porfilio, E. A., Ward, L. A., Lawson, M. A., Macpherson, A. J., McCoy, K. D., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45563 · Cited by 284
Switch Transcripts in Immunoglobulin Class Switching
Lorenz, M. G. O., Jung, S., & Radbruch, A. (1995) · Science · doi:10.1126/science.7892607 · Cited by 252
Hauer, J., Püschner, S., Ramakrishnan, P., Simon, U., Bongers, M., Federle, C., & Engelmann, H. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500187102 · Cited by 242
Prominent Role for Plasmacytoid Dendritic Cells in Mucosal T Cell-Independent IgA Induction
Tezuka, H., Abe, Y., Asano, J., Sato, T., Liu, J., Iwata, M., & Ohteki, T. (2011) · Immunity · doi:10.1016/j.immuni.2011.02.002 · Cited by 222
Tonic B cell antigen receptor signals supply an NF-κB substrate for prosurvival BLyS signaling
Stadanlick, J. E., Kaileh, M., Karnell, F. G., Scholz, J. L., Miller, J. P., Quinn, W. J., Brezski, R. J., Treml, L. S., Jordan, K. A., Monroe, J. G., et al. (2008) · Nature Immunology · doi:10.1038/ni.1666 · Cited by 210
Regulation of T cell development by the deubiquitinating enzyme CYLD
Reiley, W. W., Zhang, M., Jin, W., Losiewicz, M., Donohue, K. B., Norbury, C. C., & Sun, S.-C. (2006) · Nature Immunology · doi:10.1038/ni1315 · Cited by 198
Self-citationRegulation of the Deubiquitinating Enzyme CYLD by IκB Kinase Gamma-Dependent Phosphorylation
Reiley, W. W., Zhang, M., Wu, X., Granger, E. L., & Sun, S. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.10.3886-3895.2005 · Cited by 193
Self-citationThe IKK-related kinases: from innate immunity to oncogenesis
Clément, J.-F., Meloche, S., & Servant, M. J. (2008) · Cell Research · doi:10.1038/cr.2008.273 · Cited by 189
Sun, S., Ganchi, P. A., Beraud, C., Ballard, D. W., & Greene, W. C. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.4.1346 · Cited by 175
Self-citationTACI, an enigmatic BAFF/APRIL receptor, with new unappreciated biochemical and biological properties
Mackay, F., & Schneider, P. (2008) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2008.04.006 · Cited by 171
Kopp, E. B. (2004) · Medical Entomology and Zoology · Cited by 160
Uhlik, M. T., Good, L., Xiao, G., Harhaj, E. W., Zandi, E., Karin, M., & Sun, S. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.33.21132 · Cited by 154
Self-citationClark, K., Takeuchi, O., Akira, S., & Cohen, P. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1114194108 · Cited by 135
TACI regulates IgA production by APRIL in collaboration with HSPG
Sakurai, D., Hase, H., Kanno, Y., Kojima, H., Okumura, K., & Kobata, T. (2006) · Blood · doi:10.1182/blood-2006-08-041772 · Cited by 127
Razani, B., Zarnegar, B. J., Ytterberg, A. J., Shiba, T. L., Dempsey, P. W., Ware, C. F., Loo, J. A., & Cheng, G. (2010) · Science Signaling · doi:10.1126/scisignal.2000778 · Cited by 126
Wang, J. H., Anders, R. A., Wu, Q., Peng, D., Cho, J. H., Sun, Y., Karaliukas, R., Kang, H.-S., Turner, J. R., & Fu, Y. (2004) · Journal of Clinical Investigation · doi:10.1172/jci20096 · Cited by 125
A role for BLyS in the activation of innate immune cells
Chang, S. K., Arendt, B. K., Darce, J. R., Wu, X., & Jelinek, D. F. (2006) · Blood · doi:10.1182/blood-2005-12-017319 · Cited by 120
Snapper, C. M., Rosas, F. R., Zelazowski, P., Moorman, M. A., Kehry, M. R., Bravo, R., & Weih, F. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.184.4.1537 · Cited by 106
McCarthy, D. D., Chiu, S., Gao, Y., deLuca, L. S., & Gommerman, J. L. (2006) · Cellular Immunology · doi:10.1016/j.cellimm.2006.08.002 · Cited by 87
A Novel Mutation in the Nfkb2 Gene Generates an NF-κB2 “Super Repressor”
Tucker, E. J., O’Donnell, K., Fuchsberger, M., Hilton, A. A., Metcalf, D., Greig, K. T., Sims, N. A., Quinn, J. M. W., Alexander, W. S., Hilton, D. J., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.11.7514 · Cited by 79
Self-citationTNF受容体(TNFR)関連因子(TRAF)3はTRAF結合性TNFRによる非定型的NFκB経路のTRAF2/5介在性活性化の阻害物質として働く
Hauer, J., Püschner, S., Ramakrishnan, P., Simon, U., Bongers, M., Federle, C., & Engelmann, H. (2005) · Cited by 58
Two distinctive pathways for recruitment of naïve and primed IgM + B cells to the gut lamina propria
Suzuki, K., Meek, B., Doi, Y., Honjo, T., & Fagarasan, S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409539102 · Cited by 44
Negative Regulation of the Nuclear Factor κB-inducing Kinase by a cis-Acting Domain
Xiao, G., & Sun, S.-C. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002552200 · Cited by 43
Self-citationDysfunctions of the Iga system: a common link between intestinal and renal diseases
Papista, C., Berthelot, L., & Monteiro, R. C. (2011) · Cellular and Molecular Immunology · doi:10.1038/cmi.2010.69 · Cited by 37
IgA nephropathy: lessons from an animal model, the ddY mouse
Tomino, Y. (2008) · Journal of Nephrology · doi:10.1093/joneph/21.4.463 · Cited by 36
IL-4-induced AID expression and its relevance to IgA class switch recombination
Kim, R., Kim, H.-A., Park, J., Park, S., Jeon, S.-H., Seo, G., Seo, D. W., Seo, S. R., Chun, G., Kim, N., et al. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.07.022 · Cited by 24
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Metadata
- Authors
- Jin, J., Xiao, Y., Chang, J.-H., Yu, J., Hu, H., Starr, R., Brittain, G. C., Chang, M., Cheng, X., & Sun, S.-C.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- St Vincents Institute of Medical Research (AU)
- Corresponding author
- Sun, Shao-Cong
- Venue
- Nature Immunology
- Published
- 2012-09-30
- Volume
- 13
- Issue
- 11
- Pages
- 1101-1109
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC3477307
- OpenAlex
- W2461505078
- Cited by
- 136
- References
- 53
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 8 · 2023: 10 · 2022: 15 · 2021: 12 · 2020: 12 · 2019: 12 · 2018: 15 · 2017: 7 · 2016: 6 · 2015: 10 · 2014: 5 · 2013: 8 · 2012: 2
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Update notices
- correction (2020-07-03)
- Open access
- green
- europepmc.org
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Amgen
- National Cancer Institute (T32CA009598, P30CA016672)
- National Institute of General Medical Sciences (R01GM084459, GM084459)
- National Institute of Allergy and Infectious Diseases (AI064639, R01AI057555, R37AI064639, R01AI064639, AI057555)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- TBK1, IgA class switching, non-canonical NF-κB signaling, NIK, B cells, humoral immunity, antibody isotype switching
- MeSH terms
- NF-kappaB-Inducing Kinase, Animals, B-Lymphocytes, Gene Expression Regulation, Glomerulonephritis, IGA, Immunoglobulin A, Phosphorylation, Signal Transduction, NF-kappa B, Protein Serine-Threonine Kinases, Gene Deletion, Immunoglobulin Class Switching, Mice, Knockout, Mice, Proteolysis
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