Background: Interleukin-10 (IL-10) is a pleiotropic cytokine, which has both regulatory and stimulatory effects on different immune cell types. Different studies have reported the importance of IL-10 and Transforming growth factor-beta (TGF-p) in the regulation of B cell class switching the production of immunoglobulin A (IgA); however, the underlying mechanisms remain to be fully elucidated. The objective of this study was to investigate the TGF-p response during B stimulation of human B cells by IL-10. Methods: Pan B cells of healthy donors were negatively purified by a magnetic cell separation technique. B cells were cultured with multimeric CD40 ligand (mCD40L) and IL-10 for two and seven days. After harvesting in specific days, TGF-p receptor II and surface IgA expression was determined by flow cytometry, while IgA and TGF-p secretion was assessed by enzyme-linked immunosorbent assay. Results: B cells endogenously expressed TGF-p receptor II and after 48 hours cultivation with mCD40L or mCD40L plus IL-10, both the expression of this receptor and the production of TGF-p were significantly increased. Notably, TGF-p levels following stimulation with mCD40L and IL-10 were higher than those produced by B cells stimulated with mCD40L alone. Furthermore, at day 7 and following IL-10 stimulation, there was a significant rise in the amount of IgA secretion by class-switched plasma cells, which was higher than stimulation with mCD40L alone. Conclusion: Our findings suggest that IL-10 can modulate TGF-p production and TGF-p receptor expression in mCD40-activated human B lymphocytes.
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Heldin CH, Moustakas A. Signaling receptors for TGF-beta family members. Cold Spring Harb Perspect Biol 2016; 8(8): a022053.
Pircher R, Jullien P, Lawrence DA. Beta-transforming growth factor is stored in human blood platelets as a. atent high molecular weight complex. Biochem Biophys Res Commun 1986; 136(1):30–7.
Lawrence DA. Latent-TGF-beta: an overview. Mol Cell Biochem 2001; 219(1-2):163–70.
Schultz-Cherry S, Ribeiro S, Gentry L, Murphy-Ullrich JE. Thrombospondin binds and activates the small and large forms of latent transforming growth factor-beta in a. hemically defined system. J Biol Chem 1994; 269(43):26775–82.
Millan FA, Denhez F, Kondaiah P, Akhurst RJ. Embryonic gene expression patterns of TGF beta 1, beta 2 and beta 3 suggest different developmental functions in vivo. Development 1991; 111(1):131–43.
Gatza CE, Oh SY, Blobe GC. Roles for the type III TGF-b receptor in human cancer. Cell Signal 2010; 22(8): 1163–74.
Massague J. A. ery private TGF-b receptor embrace. Mol Cell 2008; 29(2): 149–50.
Aazami H, Seif F, Ghalehbaghi B, et al. Levels of total IgA and IgA subclasses in the serum of chronic rhinosinusitis patients. Med J. am Repub Iran 2018; 32:94.
Chen W, ten Dijke P. Immunoregulation by members of the TGFb superfamily. Nat Rev Immunol 2016; 16(12):723.
Bagheri Y, Sanaei R, Yazdani R, et al. The heterogeneous pathogenesis of selective immunoglobulin A. eficiency. Int Arch Allergy Immunol 2019; 179(3):232–46.
Santibanez JF, Quintanilla M, Bernabeu C. TGF-beta/TGF-beta receptor system and its role in physiological and pathological conditions. Clin Sci (Lond) 2011; 121(6):233–51.
Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001; 19:683–765.
Conti P, Kempuraj D, Kandere K, et al. IL-10, an inflammatory/ inhibitory cytokine, but not always. Immunol Lett 2003; 86 (2): 123–9.
Rousset F, Garcia E, Defrance T, et al. Interleukin 10 is a. otent growth and differentiation factor for activated human B. ymphocytes. Proc Natl Acad Sci USA 1992; 89 (5): 1890–3.
Burdin N, Van Kooten C, Galibert L, et al. Endogenous IL-6 and IL-10 contribute to the differentiation of CD40-activated human B. ymphocytes. J Immunol 1995; 154(6):2533–44.
Heine G, Drozdenko G, Grun JR, Chang HD, Radbruch A, Worm M. Autocrine IL-10 promotes human B-cell differentiation into IgM- or IgG-secreting plasmablasts. Eur J. mmunol 2014;44(6):1615–21.
Defrance T, Vanbervliet B, Briere F, Durand I, Rousset F, Banchereau J. Interleukin 10 and transforming growth factor beta cooperate to induce anti-CD40-activated naive human B. ells to secrete immunoglobulin A. J Exp Med 1992; 175(3): 671–82.
Mocellin S, Panelli MC, Wang E, Nagorsen D, Marincola FM. The dual role of IL-10. Trends Immunol 2003; 24(1): 36–43.
Liu Y, Wei SH, Ho AS, de Waal Malefyt R, Moore KW. Expression cloning and characterization of a. uman IL-10 receptor. J Immunol 1994; 152(4):1821–9.
Tan JC, Indelicate SR, Narula SK, Zavodny PJ, Chou CC. Characterization of interleukin-10 receptors on human and mouse cells. J Biol Chem 1993; 268(28):21053–9.
Kato H, Whiteside TL. Expression of IL-10 and IL-10 receptors on peripheral blood lymphocytes and monocytes in human head and neck squamous cell carcinoma. Tokai J. xp Clin Med 2011: 36(4):144–51.
Dennler S, Goumans MJ, ten Dijke P. Transforming growth factor beta signal transduction. J. Leukoc Biol 2002; 71(5): 731–40.
Zan H, Cerutti A, Dramitinos P, Schaffer A, Casali P. CD40 engagement triggers switching to IgAl and IgA2 in human B. ells through induction of endogenous TGF-b: evidence for TGF-b but not IL-10-dependent direct Sm → Sa. nd sequential Sm → Sg, Sg → Sa. NA. ecombination. J Immunol 1998; 161 (10):5217–25.
Garcia-Marquez MA, Shimabukuro-Vornhagen A, Theurich S, et al. A multimerized form of recombinant human CD40 ligand supports long-term activation and proliferation of B. ells. Cytotherapy 2014; 16(11): 1537–44.
Cerutti A. The regulation of IgA class switching. Nat Rev Immunol 2008; 8(6):421–34.
Islam KB, Nilsson L, Sideras P, Hammarstrom L, Smith CI. TGF-beta 1 induces germ-line transcripts of both IgA subclasses in human B. ymphocytes. Int Immunol 1991; 3(11): 1099–106.
Kehrl JH, Roberts AB, Wakefield LM, Jakowlew S, Sporn MB, Fauci AS. Transforming growth factor beta is an important immunomodulatory protein for human B. ymphocytes. J Immunol 1986; 137(12):3855–60.
Cottrez F, Groux H. Regulation of TGF-beta response during T. ell activation is modulated by IL-10. J Immunol 2001; 167 (2):773–8.
Walter MR. The molecular basis of IL-10 function: from receptor structure to the onset of signaling. Curr Top Microbiol Immunol 2014; 380: 191–212.
Behniafard N, Amirzargar A, Gharagozlou M, et al. Single nucleotide polymorphisms of the genes encoding IL-10 and TGF-bl in Iranian children with atopic dermatitis. Allergol Immunopathol 2018; 46(2): 155–9.
Tavakol M, Movahedi M, Amirzargar AA, et al. Association of interleukin 10 and transforming growth factor b. ene polymorphisms with chronic idiopathic urticaria. Acta Dermatovenerol Croat 2014; 22(4):239.
Rezaei N, Aghamohammadi A, Shakiba Y, et al. Cytokine gene polymorphisms in common variable immunodeficiency. Int Arch Allergy Immunol 2009; 150(1):1–7.
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Bagheri, Y., Babaha, F., Falak, R. et al. IL-10 induces TGF-β secretion, TGF-β receptor II upregulation, and IgA secretion in B cells. Eur Cytokine Netw 30, 107–113 (2019). https://doi.org/10.1684/ecn.2019.0434
- immunoglobulin A
- transforming growth factor-beta
- class switching