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European Journal of Medical Research
Published in: European Journal of Medical Research 1/2019

Open Access 01-12-2019 | Research

Dok-3 deficient mice display different immune clustering and Tim-3 expression

Authors: Wenjiang Yan, Yijia Tian, Peng Sun, Jingjing Yang, Na Li, Yuanyuan Sun, Shuangxi Wang, Cheng Zhang

Published in: European Journal of Medical Research | Issue 1/2019

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Abstract

Background

Dok-3 has been shown to play an important role in immune system. Tim-3 also has been recognized as an important immune regulator which involves in many diseases. The relationship of them is still unclear.

Methods

We detected the expression of Tim-3 on spleen immune cells from Dok-3 deficient mice and control mice by flow cytometry.

Results

In this article, we found that Dok-3−/− mice display almost entirely different immune clustering characteristics compared with wild type 129 mice. The CD4 T cells and CD8 T cells decreased and DC cells, macrophages, MDSCs increased when the Dok-3 gene knocked-out. The Tim-3 expression on CD4 T cells, CD8 T cells, NK cells, DC cells increased when the Dok-3 gene knocked-out. The macrophages and MDSCs just display the opposite results.

Conclusions

Although Dok-3−/− mice display different immune clustering and Tim-3 expression, the mechanism still needs further study.
Appendix
Available only for authorised users
Literature
1.
Mashima R, Hishida Y, Tezuka T, Yamanashi Y. The roles of Dok family adapters in immunoreceptor signaling. Immunol Rev. 2009;232(1):273–85.CrossRef
2.
Favre C, Gérard A, Clauzier E, Pontarotti P, Olive D, Nunès JA. DOK4 and DOK5: new Dok-related genes expressed in human T cells. Genes Immun. 2003;4(1):40–5.CrossRef
3.
Berger AH, Niki M, Morotti A, et al. Identification of DOK genes as lung tumor suppressors. Nat Genet. 2010;42(3):216–23.CrossRef
4.
Mashima R, Honda K, Yang Y, et al. Mice lacking Dok-1, Dok-2, and Dok-3 succumb to aggressive histiocytic sarcoma. Lab Invest. 2010;90(9):1357–64.CrossRef
5.
Stork B, Neumann K, Goldbeck I, et al. Subcellular localization of Grb2 by the adaptor protein Dok-3 restricts the intensity of Ca2+ signaling in B cells. EMBO J. 2007;26(4):1140–9.CrossRef
6.
Robson JD, Davidson D, Veillette A. Inhibition of the Jun N-terminal protein kinase pathway by SHIP-1, a lipid phosphatase that interacts with the adaptor molecule Dok-3. Mol Cell Biol. 2004;24(6):2332–43.CrossRef
7.
Peng Q, O’Loughlin JL, Humphrey MB. DOK3 negatively regulates LPS responses and endotoxin tolerance. PLoS ONE. 2012;7(6):e39967.CrossRef
8.
Kim SS, Lee KG, Chin CS, et al. DOK3 is required for IFN-β production by enabling TRAF3/TBK1 complex formation and IRF3 activation. J Immunol. 2014;193(2):840–8.CrossRef
9.
Sabatos CA, Chakravarti S, Cha E, et al. Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance. Nat Immunol. 2003;4(11):1102–10.CrossRef
10.
Sánchez-Fueyo A, Tian J, Picarella D, et al. Tim-3 inhibits T helper type 1-mediated auto- and alloimmune responses and promotes immunological tolerance. Nat Immunol. 2003;4(11):1093–101.CrossRef
11.
Liberal R, Grant CR, Holder BS, et al. The impaired immune regulation of autoimmune hepatitis is linked to a defective galectin-9/tim-3 pathway. Hepatology. 2012;56(2):677–86.CrossRef
12.
Wu W, Shi Y, Li S, et al. Blockade of Tim-3 signaling restores the virus-specific CD8+ T-cell response in patients with chronic hepatitis B. Eur J Immunol. 2012;42(5):1180–91.CrossRef
13.
Monney L, Sabatos CA, Gaglia JL, et al. Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature. 2002;415(6871):536–41.CrossRef
14.
Zhang Y, Ma CJ, Wang JM, et al. Tim-3 negatively regulates IL-12 expression by monocytes in HCV infection. PLoS ONE. 2011;6(5):e19664.CrossRef
15.
Chiba S, Baghdadi M, Akiba H, et al. Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat Immunol. 2012;13(9):832–42.CrossRef
16.
Ndhlovu LC, Lopez-Vergès S, Barbour JD, et al. Tim-3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity. Blood. 2012;119(16):3734–43.CrossRef
17.
Anderson AC. Tim-3, a negative regulator of anti-tumor immunity. Curr Opin Immunol. 2012;24(2):213–6.CrossRef
18.
Kang CW, Dutta A, Chang LY, et al. Apoptosis of tumor infiltrating effector TIM-3+ CD8+ T cells in colon cancer. Sci Rep. 2015;5:15659.CrossRef
Metadata
Title
Dok-3 deficient mice display different immune clustering and Tim-3 expression
Authors
Wenjiang Yan
Yijia Tian
Peng Sun
Jingjing Yang
Na Li
Yuanyuan Sun
Shuangxi Wang
Cheng Zhang
Publication date
01-12-2019
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2019
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-019-0384-7

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