Adiponectin-expressing Treg Facilitate T Lymphocyte Development in Thymic Nurse Cell Complexes

Overview

Journal Commun Biol

Specialty Biology

Date 2021 Mar 17

PMID 33727658

Citations 11

Authors

Yiwei Zhang

Handi Cao

Jie Chen

Yuanxin Li

Aimin Xu

Yu Wang

Affiliations

Soon will be listed here.

Abstract

Adiponectin is a well-known insulin sensitizer and anti-inflammatory molecule, possessing therapeutic potentials in cardiovascular, metabolic and cancer diseases. Results of the present study demonstrate that adiponectin is expressed in a population of regulatory T-cells (Treg) resided within the thymic nurse cell (TNC) complexes. Adoptive transfer of adiponectin-expressing Treg precursors effectively attenuated obesity, improved glucose and insulin tolerance, prevented fatty liver injuries in wild-type mice fed a high-fat diet, and significantly inhibited breast cancer development in MMTV-PyVT transgenic mice. Within the TNC complexes, locally produced adiponectin bound to and regulated the expression as well as the distribution of CD100, a transmembrane lymphocyte semaphorin, in turn modulating the lymphoepithelial interactions to facilitate T-cell development and maturation. In summary, adiponectin plays an important role in the selection and development of T lymphocytes within the TNC complexes. Adiponectin-expressing Treg represent a promising candidate for adoptive cell immunotherapy against obesity-related metabolic and cancer diseases.

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References

Wang Y, Lam K, Xu J, Lu G, Xu L, Cooper G . Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerization-dependent manner. J Biol Chem. 2005; 280(18):18341-7. DOI: 10.1074/jbc.M501149200. View

Yano H, Andrews L, Workman C, Vignali D . Intratumoral regulatory T cells: markers, subsets and their impact on anti-tumor immunity. Immunology. 2019; 157(3):232-247. PMC: 6587321. DOI: 10.1111/imm.13067. View

Shi H, Chi H . Metabolic Control of Treg Cell Stability, Plasticity, and Tissue-Specific Heterogeneity. Front Immunol. 2020; 10:2716. PMC: 6917616. DOI: 10.3389/fimmu.2019.02716. View

Perry J, Hsieh C . Development of T-cell tolerance utilizes both cell-autonomous and cooperative presentation of self-antigen. Immunol Rev. 2016; 271(1):141-55. PMC: 4837647. DOI: 10.1111/imr.12403. View

Takahama Y, Ohigashi I, Baik S, Anderson G . Generation of diversity in thymic epithelial cells. Nat Rev Immunol. 2017; 17(5):295-305. DOI: 10.1038/nri.2017.12. View

Xu A, Wang Y, Keshaw H, Xu L, Lam K, Cooper G . The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. J Clin Invest. 2003; 112(1):91-100. PMC: 162288. DOI: 10.1172/JCI17797. View

Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K . The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001; 7(8):941-6. DOI: 10.1038/90984. View

Stern J, Rutkowski J, Scherer P . Adiponectin, Leptin, and Fatty Acids in the Maintenance of Metabolic Homeostasis through Adipose Tissue Crosstalk. Cell Metab. 2016; 23(5):770-84. PMC: 4864949. DOI: 10.1016/j.cmet.2016.04.011. View

Samms M, Philp D, Emanus F, Osuji O, Pezzano M, Guyden J . Lysosomal-mediated degradation of apoptotic thymocytes within thymic nurse cells. Cell Immunol. 1999; 197(2):108-15. DOI: 10.1006/cimm.1999.1559. View

10.

Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J . Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999; 257(1):79-83. DOI: 10.1006/bbrc.1999.0255. View

11.

Hansenne I, Louis C, Martens H, Dorban G, Charlet-Renard C, Peterson P . Aire and Foxp3 expression in a particular microenvironment for T cell differentiation. Neuroimmunomodulation. 2008; 16(1):35-44. DOI: 10.1159/000179665. View

12.

Rajabinejad M, Asadi G, Ranjbar S, Afshar Hezarkhani L, Salari F, Gorgin Karaji A . Semaphorin 4A, 4C, and 4D: Function comparison in the autoimmunity, allergy, and cancer. Gene. 2020; 746:144637. DOI: 10.1016/j.gene.2020.144637. View

13.

Rodriguez-Perea A, Arcia E, Rueda C, Velilla P . Phenotypical characterization of regulatory T cells in humans and rodents. Clin Exp Immunol. 2016; 185(3):281-91. PMC: 4991523. DOI: 10.1111/cei.12804. View

14.

Franks S, Cambier J . Putting on the Brakes: Regulatory Kinases and Phosphatases Maintaining B Cell Anergy. Front Immunol. 2018; 9:665. PMC: 5897502. DOI: 10.3389/fimmu.2018.00665. View

15.

Nakagawa Y, Ohigashi I, Nitta T, Sakata M, Tanaka K, Murata S . Thymic nurse cells provide microenvironment for secondary T cell receptor α rearrangement in cortical thymocytes. Proc Natl Acad Sci U S A. 2012; 109(50):20572-7. PMC: 3528577. DOI: 10.1073/pnas.1213069109. View

16.

Hui X, Gu P, Zhang J, Nie T, Pan Y, Wu D . Adiponectin Enhances Cold-Induced Browning of Subcutaneous Adipose Tissue via Promoting M2 Macrophage Proliferation. Cell Metab. 2015; 22(2):279-90. DOI: 10.1016/j.cmet.2015.06.004. View

17.

Kleiner D, Brunt E, Van Natta M, Behling C, Contos M, Cummings O . Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005; 41(6):1313-21. DOI: 10.1002/hep.20701. View

18.

Delgoffe G, Woo S, Turnis M, Gravano D, Guy C, Overacre A . Stability and function of regulatory T cells is maintained by a neuropilin-1-semaphorin-4a axis. Nature. 2013; 501(7466):252-6. PMC: 3867145. DOI: 10.1038/nature12428. View

19.

Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N . Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood. 2000; 96(5):1723-32. View

20.

Villa-Verde D, Silva-Monteiro E, Jasiulionis M, Farias-de-Oliveira D, Brentani R, Savino W . Galectin-3 modulates carbohydrate-dependent thymocyte interactions with the thymic microenvironment. Eur J Immunol. 2002; 32(5):1434-44. DOI: 10.1002/1521-4141(200205)32:5<1434::AID-IMMU1434>3.0.CO;2-M. View