The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“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]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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RETRACTED ARTICLE: DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL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-citation
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–137 of 137
Workman, L. M., Zhang, L., Fan, Y., Zhang, W., & Habelhah, H. (2020) · Molecular and Cellular Biology · doi:10.1128/mcb.00429-19 · Cited by 10
Duan, W., Yi, L., Tian, Y., Huang, H.-P., Li, Z., Bi, Y., Guo, M., Li, Y., Liu, Y., Ma, Y., et al. (2021) · Molecular Neurobiology · doi:10.1007/s12035-020-02235-3 · Cited by 12
TBK1 suppression of IgA in the NIK of time
Bram, R. J. (2012) · Nature Immunology · doi:10.1038/ni.2451 · Cited by 10
Ujevic, A., Knizkova, D., Synackova, A., Přibíková, M., Trivić, T., Dalinskaya, A., Drobek, A., Niederlová, V., Paprčková, D., de Guia, R. M., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-54399-4 · Cited by 9
Carr, M., Mamand, S., Chapman, K. L., Perrior, T. R., & Wagner, S. D. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15774 · Cited by 9
TBK 1 is involved in M‐ CSF ‐induced macrophage polarization through mediating the IRF 5/ IRF 4 axis
Li, Y., Ji, L., Liu, C., Li, J., Wen, D., Li, Z., Yu, L., Guo, M., Zhang, S., Duan, W., et al. (2024) · FEBS Journal · doi:10.1111/febs.17297 · Cited by 8
Pan, L., Yang, L., Yi, Z., Zhang, W., & Gong, J. (2022) · Molecular Immunology · doi:10.1016/j.molimm.2022.04.009 · Cited by 7
NAT10-mediated acetylation of NIK mRNA in B cells promotes IgA production
Jiang, W.-J., Mao, X.-T., Li, W., Jin, N., Wang, Y., Guan, G., Jin, J., & Li, Y. (2025) · EMBO Reports · doi:10.1038/s44319-025-00509-2 · Cited by 7
Self-citationThe NF ‐ κB Signalling Pathway: Mechanisms, Consequences and Therapeutic Targets
Pourdad, B., & Pourdad, A. (2026) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.71229 · Cited by 8
Hagan, R. S., Gomez, J. C., Torres-Castillo, J. L., Martin, J. R., & Doerschuk, C. M. (2022) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2020-0311oc · Cited by 7
c-Myb Dominates TBK1-Mediated Endotoxin Tolerance in Kupffer Cells by Negatively Regulating DTX4
Wu, Y., Pan, L., Yi, Z., Zhang, W., & Gong, J. (2023) · Journal of Immunology Research · doi:10.1155/2023/5990156 · Cited by 7
Ortega, M. A., Villiger, R., Harrison-Chau, M. H., Lieu, S., Tamashiro, K., Lee, A. J., Fujimoto, B., Patwardhan, G. Y., Kepler, J. K., & Fogelgren, B. (2022) · Disease Models & Mechanisms · doi:10.1242/dmm.049785 · Cited by 5
Watanabe‐Matsui, M., Kadoya, S., Segawa, K., Shima, H., Nakagawa, T., Nagasawa, Y., Hayashi, S., Matsumoto, M., Ikeda, M., Muto, A., et al. (2022) · iScience · doi:10.1016/j.isci.2024.111529 · Cited by 7
Kaaij, M. H., Rip, J., Jeucken, K. C. M., Kan, Y. Y., van Rooijen, C. C. N., Saris, J., Pots, D., Frey, S., Grootjans, J., Schett, G. A., et al. (2021) · The Journal of Immunology · doi:10.4049/jimmunol.2100512 · Cited by 6
Almeida, M. S., Bezbradica, J. S., & Coban, C. (2026) · Current Opinion in Virology · doi:10.1016/j.coviro.2026.101545 · Cited by 4
Splenic Architecture and Function Requires Tight Control of Transmembrane TNF Expression
Jeucken, K. C. M., Kaaij, M. H., Rip, J., van Rooijen, C. C. N., Kan, Y. Y., Corneth, O. B. J., van Hamburg, J. P., & Tas, S. W. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23042229 · Cited by 4
Expression profiling pre‐diabetic mice to uncover drugs with clinical application to type 1 diabetes
Pang, D., Irvine, K. M., Mehdi, A. M., Thomas, H. E., Harris, M. A., Hamilton‐Williams, E. E., & Thomas, R. (2015) · Clinical & Translational Immunology · doi:10.1038/cti.2015.17 · Cited by 3
B cell-intrinsic DNase1L3 is essential for the T cell-independent type II response in mice
Kato, K., Haniuda, K., Fukao, S., & Kitamura, D. (2023) · International Immunology · doi:10.1093/intimm/dxad001 · Cited by 4
Björk, A., Wahadat, M. J., Sánchez-Blázquez, M., Braams, M., Rip, J., van Tilburg, S. J., van Helden-Meeuwsen, C. G., Kamphuis, S. S. M., van den Bosch, T. P. P., Brkić, Z., et al. (2025) · RMD Open · doi:10.1136/rmdopen-2024-005351 · Cited by 3
The role of protein phosphorylation in the regulation of class switch recombination
Tanabe, K., & Kajihara, R. (2020) · Biocell · doi:10.32604/biocell.2020.012740 · Cited by 1
Regulation of immunological tolerance and human autoimmunity by NF-κB
Cook, M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822564-6.00019-7 · Cited by 1
Zhou, X., Jia, Z., De, X., Yang, Z., Li, Y., Liu, R., Niu, L., Yao, X., Jiang, Y., Wang, F., et al. (2026) · Microorganisms · doi:10.3390/microorganisms14010180 · Cited by 1
The NF-κB-inducing kinase: a central regulator of immunity and autoimmune diseases
Yu, L., 毛宏梅, & Sun, S. (2026) · Immunity & Inflammation · doi:10.1007/s44466-026-00026-4 · Cited by 1
Self-citationB cells in systemic lupus erythematosus: from pathogenic mechanisms to targeted therapies
Su, X., Lei, Q., Chen, X., Tong, Y., Liu, S., Guo, Y., Yang, W., Yu, H., & Lin, L. (2026) · Autoimmunity Reviews · doi:10.1016/j.autrev.2026.104079 · Cited by 1
Regulation of IgA production by TBK1 prevents nephropathy
Carney, E. F. (2012) · Nature Reviews Nephrology · doi:10.1038/nrneph.2012.226
TRAF Protein Function in Noncanonical NF-κB Signaling
Reichardt, A. D., Pindado, J., Zaver, S. A., & Cheng, G. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-2422-6_14
James, K. R. (2017) · The University of Queensland · doi:10.14264/uql.2017.339
Flores, S. K. (2016) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.42.2016.tde-11112016-134322
Schlechter, N. (2017) · SUNScholar (Stellenbosch University)
Characterization of Biomedical and Incidental Nanoparticles in the Lungs and Their Effects on Health
McDaniel, D. K. (2018) · VTechWorks (Virginia Tech)
Johannes, N., & Maunga, P. (2023) · STEMedicine · doi:10.37175/stemedicine.v4.i1.159
Wang, X., Zhang, J., Chen, J., Huang, Q., Duan, X., & Zhu, W. (2026) · Viruses · doi:10.3390/v18030310
Phan, T., Mavigner, M., Dashti, A., Chahroudi, A., Ribeiro, R. M., Ke, R., & Perelson, A. S. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.01.729198
Martinello, C., Krug, A., Marin-Escudero, P., Pollet, A., Lemonnier, F., Boyer, L., & Verhoeyen, E. (2026) · Pharmaceutics · doi:10.3390/pharmaceutics18101292
BindingDB Entry 50008147: Discovery of GSK8612, a Highly Selective and Potent TBK1 Inhibitor.
BindingDB (2021) · UC San Diego · doi:10.7270/q21n84hw
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
