Interleukin-10 production and T cell-suppressive capacity in B cell subsets from atherosclerotic apoE −/− mice | springermedicine.com

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01-10-2017 | Original Article

Interleukin-10 production and T cell-suppressive capacity in B cell subsets from atherosclerotic apoE ^−/− mice

Authors: Héctor Rincón-Arévalo, Janny Villa-Pulgarín, Jorge Tabares, Mauricio Rojas, Gloria Vásquez, José R. Ramírez-Pineda, Diana Castaño, Lina M. Yassin

Published in: Immunologic Research | Issue 5/2017

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Abstract

The evidence regarding the role of regulatory B cells (Breg) in atherosclerosis are scarce, and there are contradictory data about their atheroprotective properties. Due to the demonstrated protective function of Breg in different inflammatory diseases mainly through interleukin-10 (IL-10) production, the knowledge of their participation in atherosclerosis immunopathology would be very valuable. To further study which B cell subsets participate in IL-10 production and their regulatory role, splenocytes from apolipoprotein-E-deficient mice were evaluated by ex vivo and in vitro cultures. Atherosclerotic mice had increased frequency of IL-10⁺ B cells, which presented high CD1d, CD19, and IgM, but variable CD5, CD21, and CD23 expression. IL-10⁺ B cells were not enriched in B cell subsets previously reported as Breg. Increased frequency of IL-10⁺ B cells with transitional 1-like (T1-like) and follicular (FO) and reduced CD5⁺ and marginal zone (MZ) phenotypes were observed ex vivo. Increased frequency of IL-10⁺ B cells with T1-like and MZ, and decreased IL-10⁺ FO and T2 phenotypes were also observed in vitro. To determine regulatory capacity of B cells in the atherosclerotic model, each subset were co-cultured with CD4⁺CD25⁻ T cells. CD5⁺, FO, MZ, and T1-like cells from atherosclerotic mice exhibited regulation in an IL-10-dependent manner. However, only FO cells decreased both frequency of interferon gamma (IFN-γ)⁺ and tumor necrosis factor alpha (TNF-α)⁺ and proliferation of T cells. Finally, splenocytes showed increased frequency of IFN-γ⁺ and TNF-α⁺ cells only when FO-depleted B cells were evaluated. These results suggest that mainly FO B cells can modulate in some level the inflammatory responses observed in atherosclerosis.

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1.

World Health Organization. World Health Statistics. Geneva: World Health Organization; 2013.

2.

Hansson GK, Hermansson A. The immune system in atherosclerosis. Nat Immunol. 2011;12(3):204–12. doi:10.1038/ni.2001.CrossRefPubMed

3.

McCarthy C, Duffy MM, Mooney D, James WG, Griffin MD, Fitzgerald DJ, et al. IL-10 mediates the immunoregulatory response in conjugated linoleic acid-induced regression of atherosclerosis. FASEB J: Off Publ Fed Am Soc Exp Biol. 2013;27(2):499–510. doi:10.1096/fj.12-215442.CrossRef

4.

Pinderski LJ, Fischbein MP, Subbanagounder G, Fishbein MC, Kubo N, Cheroutre H, et al. Overexpression of interleukin-10 by activated T lymphocytes inhibits atherosclerosis in LDL receptor-deficient mice by altering lymphocyte and macrophage phenotypes. Circ Res. 2002;90(10):1064–71.CrossRefPubMed

5.

Han X, Kitamoto S, Wang H, Boisvert WA. Interleukin-10 overexpression in macrophages suppresses atherosclerosis in hyperlipidemic mice. FASEB J: Off Publ Fed Am Soc Exp Biol. 2010;24(8):2869–80. doi:10.1096/fj.09-148155.CrossRef

6.

Caligiuri G, Rudling M, Ollivier V, Jacob MP, Michel JB, Hansson GK, et al. Interleukin-10 deficiency increases atherosclerosis, thrombosis, and low-density lipoproteins in apolipoprotein E knockout mice. Mol Med. 2003;9(1–2):10–7.PubMedPubMedCentral

7.

Potteaux S, Esposito B, van Oostrom O, Brun V, Ardouin P, Groux H, et al. Leukocyte-derived interleukin 10 is required for protection against atherosclerosis in low-density lipoprotein receptor knockout mice. Arterioscler Thromb Vasc Biol. 2004;24(8):1474–8. doi:10.1161/01.ATV.0000134378.86443.cd.CrossRefPubMed

8.

Fillatreau S, Sweenie CH, McGeachy MJ, Gray D, Anderton SM. B cells regulate autoimmunity by provision of IL-10. Nat Immunol. 2002;3(10):944–50. doi:10.1038/ni833.CrossRefPubMed

9.

Caligiuri G, Nicoletti A, Poirier B, Hansson GK. Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice. J Clin Invest. 2002;109(6):745–53. doi:10.1172/JCI7272.CrossRefPubMedPubMedCentral

10.

Galkina E, Kadl A, Sanders J, Varughese D, Sarembock IJ, Ley K. Lymphocyte recruitment into the aortic wall before and during development of atherosclerosis is partially L-selectin dependent. J Exp Med. 2006;203(5):1273–82. doi:10.1084/jem.20052205.CrossRefPubMedPubMedCentral

11.

Doran AC, Lipinski MJ, Oldham SN, Garmey JC, Campbell KA, Skaflen MD, et al. B-cell aortic homing and atheroprotection depend on Id3. Circ Res. 2012;110(1):e1–12. doi:10.1161/CIRCRESAHA.111.256438.CrossRefPubMed

12.

Gjurich BN, Taghavie-Moghadam PL, Ley K, Galkina EV. L-selectin deficiency decreases aortic B1a and Breg subsets and promotes atherosclerosis. Thromb Haemost. 2014;112(4):803–11. doi:10.1160/TH13-10-0865.CrossRefPubMedPubMedCentral

13.

Major AS, Fazio S, Linton MF. B-lymphocyte deficiency increases atherosclerosis in LDL receptor-null mice. Arterioscler Thromb Vasc Biol. 2002;22(11):1892–8.CrossRefPubMed

14.

Rosenfeld SM, Perry HM, Gonen A, Prohaska TA, Srikakulapu P, Grewal S, et al. B-1b cells secrete Atheroprotective IgM and attenuate atherosclerosis. Circ Res. 2015;117(3):e28–39. doi:10.1161/CIRCRESAHA.117.306044.CrossRefPubMedPubMedCentral

15.

Kyaw T, Tay C, Krishnamurthi S, Kanellakis P, Agrotis A, Tipping P, et al. B1a B lymphocytes are atheroprotective by secreting natural IgM that increases IgM deposits and reduces necrotic cores in atherosclerotic lesions. Circ Res. 2011;109(8):830–40. doi:10.1161/CIRCRESAHA.111.248542.CrossRefPubMed

16.

Kyaw T, Tay C, Khan A, Dumouchel V, Cao A, To K, et al. Conventional B2 B cell depletion ameliorates whereas its adoptive transfer aggravates atherosclerosis. J Immunol. 2010;185(7):4410–9. doi:10.4049/jimmunol.1000033.CrossRefPubMed

17.

Lipinski MJ, Perry HM, Doran AC, Oldham SN, McNamara CA. Comment on “conventional B2 B cell depletion ameliorates whereas its adoptive transfer aggravates atherosclerosis”. J Immunol. 2011;186(1):4; author reply 6. doi:10.4049/jimmunol.1090119.CrossRefPubMed

18.

Rincón-Arévalo H, Yassin-Noreña L, Vásquez G, Castano D. Linfocitos B reguladores en enfermedades humanas y modelos murinos de autoinmunidad. Inmunología. 2013;32(4):129–38.CrossRef

19.

Rincon-Arevalo H, Sanchez-Parra CC, Castano D, Yassin L, Vasquez G. Regulatory B cells and mechanisms. Int Rev Immunol. 2015; doi:10.3109/08830185.2015.1015719.

20.

Blair PA, Chavez-Rueda KA, Evans JG, Shlomchik MJ, Eddaoudi A, Isenberg DA, et al. Selective targeting of B cells with agonistic anti-CD40 is an efficacious strategy for the generation of induced regulatory T2-like B cells and for the suppression of lupus in MRL/lpr mice. J Immunol. 2009;182(6):3492–502. doi:10.4049/jimmunol.0803052.CrossRefPubMedPubMedCentral

21.

Matsushita T, Horikawa M, Iwata Y, Tedder TF. Regulatory B cells (B10 cells) and regulatory T cells have independent roles in controlling experimental autoimmune encephalomyelitis initiation and late-phase immunopathogenesis. J Immunol. 2010;185(4):2240–52. doi:10.4049/jimmunol.1001307.CrossRefPubMedPubMedCentral

22.

Strom AC, Cross AJ, Cole JE, Blair PA, Leib C, Goddard ME, et al. B regulatory cells are increased in hypercholesterolaemic mice and protect from lesion development via IL-10. Thromb Haemost. 2015;114(4):835–47. doi:10.1160/TH14-12-1084.CrossRefPubMed

23.

Sage AP, Nus M, Baker LL, Finigan AJ, Masters LM, Mallat Z. Regulatory B cell-specific interleukin-10 is dispensable for atherosclerosis development in mice. Arterioscler Thromb Vasc Biol. 2015;35(8):1770–3. doi:10.1161/ATVBAHA.115.305568.CrossRefPubMed

24.

Rincon-Arevalo H, Castano D, Villa-Pulgarin J, Rojas M, Vasquez G, Correa LA, et al. Dyslipidemia-associated alterations in B cell subpopulation frequency and phenotype during experimental atherosclerosis. Atherosclerosis. 2016;247:118–26. doi:10.1016/j.atherosclerosis.2015.12.022.CrossRefPubMed

25.

Rincon-Arevalo H, Castano D, Villa-Pulgarin J, Rojas M, Vasquez G, Correa LA, et al. Data in support of dyslipidemia-associated alterations in B cell subpopulations frequency and phenotype during experimental atherosclerosis. Data Brief. 2016;7:958–72. doi:10.1016/j.dib.2016.02.048.CrossRefPubMedPubMedCentral

26.

Matsushita T, Tedder TF. Identifying regulatory B cells (B10 cells) that produce IL-10 in mice. Methods Mol Biol. 2011;677:99–111. doi:10.1007/978-1-60761-869-0_7.CrossRefPubMed

27.

Yoshizaki A, Miyagaki T, DiLillo DJ, Matsushita T, Horikawa M, Kountikov EI, et al. Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions. Nature. 2012;491(7423):264–8. doi:10.1038/nature11501.CrossRefPubMedPubMedCentral

28.

Yanaba K, Bouaziz JD, Matsushita T, Tsubata T, Tedder TF. The development and function of regulatory B cells expressing IL-10 (B10 cells) requires antigen receptor diversity and TLR signals. J Immunol. 2009;182(12):7459–72. doi:10.4049/jimmunol.0900270.CrossRefPubMedPubMedCentral

29.

Maseda D, Candando KM, Smith SH, Kalampokis I, Weaver CT, Plevy SE, et al. Peritoneal cavity regulatory B cells (B10 cells) modulate IFN-gamma+CD4+ T cell numbers during colitis development in mice. J Immunol. 2013;191(5):2780–95. doi:10.4049/jimmunol.1300649.CrossRefPubMedPubMedCentral

30.

Evans JG, Chavez-Rueda KA, Eddaoudi A, Meyer-Bahlburg A, Rawlings DJ, Ehrenstein MR, et al. Novel suppressive function of transitional 2 B cells in experimental arthritis. J Immunol. 2007;178(12):7868–78.CrossRefPubMed

31.

Vadasz Z, Peri R, Eiza N, Slobodin G, Balbir-Gurman A, Toubi E. The expansion of CD25 high IL-10 high FoxP3 high B regulatory cells is in association with SLE disease activity. J Immunol Res. 2015;2015:254245. doi:10.1155/2015/254245.CrossRefPubMedPubMedCentral

32.

Mauri C, Gray D, Mushtaq N, Londei M. Prevention of arthritis by interleukin 10-producing B cells. J Exp Med. 2003;197(4):489–501.CrossRefPubMedPubMedCentral

33.

Das A, Ellis G, Pallant C, Lopes AR, Khanna P, Peppa D, et al. IL-10-producing regulatory B cells in the pathogenesis of chronic hepatitis B virus infection. J Immunol. 2012;189(8):3925–35. doi:10.4049/jimmunol.1103139.CrossRefPubMedPubMedCentral

34.

Yanaba K, Bouaziz JD, Haas KM, Poe JC, Fujimoto M, Tedder TF. A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses. Immunity. 2008;28(5):639–50. doi:10.1016/j.immuni.2008.03.017.CrossRefPubMed

35.

Zhang X. Regulatory functions of innate-like B cells. Cell Mol Immunol. 2013;10(2):113–21. doi:10.1038/cmi.2012.63.CrossRefPubMedPubMedCentral

36.

Zhou LJ, Smith HM, Waldschmidt TJ, Schwarting R, Daley J, Tedder TF. Tissue-specific expression of the human CD19 gene in transgenic mice inhibits antigen-independent B-lymphocyte development. Mol Cell Biol. 1994;14(6):3884–94.CrossRefPubMedPubMedCentral

37.

Singh AR, Peirce SK, Joshi S, Durden DL. PTEN and PI-3 kinase inhibitors control LPS signaling and the lymphoproliferative response in the CD19+ B cell compartment. Exp Cell Res. 2014;327(1):78–90. doi:10.1016/j.yexcr.2014.05.016.CrossRefPubMed

38.

Moore-Connors JM, Kim HS, Marshall JS, Stadnyk AW, Halperin SA, Wang J. CD43, but not CD43, IL-10-producing CD1dCD5 B cells suppress type 1 immune responses during chlamydia muridarum genital tract infection. Mucosal Immunol. 2014; doi:10.1038/mi.2014.45.

39.

Lee CC, Kung JT. Marginal zone B cell is a major source of Il-10 in listeria monocytogenes susceptibility. J Immunol. 2012;189(7):3319–27. doi:10.4049/jimmunol.1201247.CrossRefPubMed

40.

Carter NA, Rosser EC, Mauri C. Interleukin-10 produced by B cells is crucial for the suppression of Th17/Th1 responses, induction of T regulatory type 1 cells and reduction of collagen-induced arthritis. Arthritis Res Ther. 2012;14(1):R32. doi:10.1186/ar3736.CrossRefPubMedPubMedCentral

41.

Ledesma-Soto Y, Blanco-Favela F, Fuentes-Panana EM, Tesoro-Cruz E, Hernandez-Gonzalez R, Arriaga-Pizano L, et al. Increased levels of prolactin receptor expression correlate with the early onset of lupus symptoms and increased numbers of transitional-1 B cells after prolactin treatment. BMC Immunol. 2012;13:11. doi:10.1186/1471-2172-13-11.CrossRefPubMedPubMedCentral

42.

Loder F, Mutschler B, Ray RJ, Paige CJ, Sideras P, Torres R, et al. B cell development in the spleen takes place in discrete steps and is determined by the quality of B cell receptor-derived signals. J Exp Med. 1999;190(1):75–89.CrossRefPubMedPubMedCentral

43.

Miyazaki D, Kuo CH, Tominaga T, Inoue Y, Ono SJ. Regulatory function of CpG-activated B cells in late-phase experimental allergic conjunctivitis. Invest Ophthalmol Vis Sci. 2009;50(4):1626–35. doi:10.1167/iovs.08-2701.CrossRefPubMed

44.

Meher AK, Johnston WF, Lu G, Pope NH, Bhamidipati CM, Harmon DB, et al. B2 cells suppress experimental abdominal aortic aneurysms. Am J Pathol. 2014;184(11):3130–41. doi:10.1016/j.ajpath.2014.07.006.CrossRefPubMedPubMedCentral

45.

Yoshizaki A, Tedder TF. IL-21 induces regulatory B cell differentiation and immunosuppressive effect through cognate interaction with T cells. Nihon Rinsho Men’eki Gakkai kaishi=Jpn J Clin Immunol. 2015;38(1):57–64. doi:10.2177/jsci.38.57.CrossRef

46.

Rodgers DT, Pineda MA, McGrath MA, Al-Riyami L, Harnett W, Harnett MM. Protection against collagen-induced arthritis in mice afforded by the parasitic worm product, ES-62, is associated with restoration of the levels of interleukin-10-producing B cells and reduced plasma cell infiltration of the joints. Immunology. 2014;141(3):457–66. doi:10.1111/imm.12208.CrossRefPubMedPubMedCentral

47.

Maseda D, Smith SH, DiLillo DJ, Bryant JM, Candando KM, Weaver CT, et al. Regulatory B10 cells differentiate into antibody-secreting cells after transient IL-10 production in vivo. J Immunol. 2012;188(3):1036–48. doi:10.4049/jimmunol.1102500.CrossRefPubMed

48.

Rincon-Arevalo H, Sanchez-Parra CC, Castano D, Yassin L, Vasquez G. Regulatory B cells and mechanisms. Int Rev Immunol. 2016;35(2):156–76. doi:10.3109/08830185.2015.1015719.PubMed

49.

Bilate AM, Lafaille JJ. Induced CD4+Foxp3+ regulatory T cells in immune tolerance. Annu Rev Immunol. 2012;30:733–58. doi:10.1146/annurev-immunol-020711-075043.CrossRefPubMed

Title: Interleukin-10 production and T cell-suppressive capacity in B cell subsets from atherosclerotic apoE −/− mice
Authors: Héctor Rincón-Arévalo
Janny Villa-Pulgarín
Jorge Tabares
Mauricio Rojas
Gloria Vásquez
José R. Ramírez-Pineda
Diana Castaño
Lina M. Yassin
Publication date: 01-10-2017
Publisher: Springer US
Published in: Immunologic Research / Issue 5/2017
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI: https://doi.org/10.1007/s12026-017-8939-6

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