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Comment
. 2018 Aug;15(8):743-745.
doi: 10.1038/cmi.2017.165. Epub 2018 Mar 5.

TBK1 as a regulator of autoimmunity and antitumor immunity

Jian-Hong Shi  1   2 , Xiaoping Xie  2 , Shao-Cong Sun  3
Affiliations
Comment

TBK1 as a regulator of autoimmunity and antitumor immunity

Jian-Hong Shi et al. Cell Mol Immunol. 2018 Aug.
No abstract available

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Diverse functions of TBK1. TBK1 can be activated by signals from pattern-recognition receptors (PRRs), TNF receptor (TNFR) supper family members, T cell receptor (TCR) and B cell receptor (BCR). In addition to mediating type I interferon (IFN-I) induction via phosphorylation of IRF3 and IRF7, TBK1 exerts many other functions. TBK1 phosphorylates AKT and promotes ubiquitin-dependent AKT degradation in T cells, thereby regulating T cell homeostasis and migration. TBK1 negatively regulates noncanonical NF-κB activation in B cells by promoting degradation of NIK, which is important for preventing abnormal IgA class switching. TBK1 also regulates oncogenesis and autophagy through phosphorylation of mTOR and autophagy receptors (p62 and OPTN), respectively.
Figure 2
Figure 2
TBK1 functions in DCs to regulate immune tolerance and T cell homeostasis. In wildtype (WT) DCs, TBK1 is activated by homeostatic triggers, likely cytokines and self-DNA, and phosphorylates serine 727 of STAT3. Activated STAT3 negatively regulates type I interferon (IFN-I)-mediated induction of immunostimulatory genes that are important for DC maturation and T cell activation via cross-priming. Deletion of TBK1 in DCs causes enhanced IFN-I signaling, which is associated with perturbed T cells homeostasis, autoimmunity, and enhanced antitumor immunity.
See this image and copyright information in PMC

Comment on

  • The kinase TBK1 functions in dendritic cells to regulate T cell homeostasis, autoimmunity, and antitumor immunity.
    Xiao Y, Zou Q, Xie X, Liu T, Li HS, Jie Z, Jin J, Hu H, Manyam G, Zhang L, Cheng X, Wang H, Marie I, Levy DE, Watowich SS, Sun SC. Xiao Y, et al. J Exp Med. 2017 May 1;214(5):1493-1507. doi: 10.1084/jem.20161524. Epub 2017 Mar 29. J Exp Med. 2017. PMID: 28356390 Free PMC article.
  • Ex Vivo Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids.
    Jenkins RW, Aref AR, Lizotte PH, Ivanova E, Stinson S, Zhou CW, Bowden M, Deng J, Liu H, Miao D, He MX, Walker W, Zhang G, Tian T, Cheng C, Wei Z, Palakurthi S, Bittinger M, Vitzthum H, Kim JW, Merlino A, Quinn M, Venkataramani C, Kaplan JA, Portell A, Gokhale PC, Phillips B, Smart A, Rotem A, Jones RE, Keogh L, Anguiano M, Stapleton L, Jia Z, Barzily-Rokni M, Cañadas I, Thai TC, Hammond MR, Vlahos R, Wang ES, Zhang H, Li S, Hanna GJ, Huang W, Hoang MP, Piris A, Eliane JP, Stemmer-Rachamimov AO, Cameron L, Su MJ, Shah P, Izar B, Thakuria M, LeBoeuf NR, Rabinowits G, Gunda V, Parangi S, Cleary JM, Miller BC, Kitajima S, Thummalapalli R, Miao B, Barbie TU, Sivathanu V, Wong J, Richards WG, Bueno R, Yoon CH, Miret J, Herlyn M, Garraway LA, Van Allen EM, Freeman GJ, Kirschmeier PT, Lorch JH, Ott PA, Hodi FS, Flaherty KT, Kamm RD, Boland GM, Wong KK, Dornan D, Paweletz CP, Barbie DA. Jenkins RW, et al. Cancer Discov. 2018 Feb;8(2):196-215. doi: 10.1158/2159-8290.CD-17-0833. Epub 2017 Nov 3. Cancer Discov. 2018. PMID: 29101162 Free PMC article.

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