Protein & Cell

, Volume 4, Issue 3, pp 197–210 | Cite as

Immune modulatory function of abundant immune-related microRNAs in microvesicles from bovine colostrum

  • Qi Sun
  • Xi Chen
  • Jianxiong Yu
  • Ke Zen
  • Chen-Yu Zhang
  • Liang Li
Research Article


Colostrum provides essential nutrients and immunologically active factors that are beneficial to newborns. Our previous work demonstrated that milk contains large amounts of miRNA that is largely stored in milk-derived microvesicles (MVs). In the present study, we found that the MVs from colostrum contain significantly higher levels of several immune-related miRNAs. We hypothesized that the colostrum MVs may transfer the immune-related miRNAs into cells, which contribute to its immune modulatory feature. We isolated colostrum MVs by ultracentrifugation and demonstrated several immune modulation features associated with miRNAs. We also provide evidence that the physical structure of milk-derived MVs is essential for transfer miRNAs and following immune modulation effect. Moreover, we found that colostrum powder-derived MVs also contains higher levels of immune-related miRNAs that display similar immune modulation effects. Taken together, these results show that MV-containing immunerelated miRNAs may be a novel mechanism by which colostrum modulates body immune response.


colostrum miRNAs microvesicles immune modulation 


  1. Admyre, C., Johansson, S.M., Qazi, K.R., Filen, J.J., Lahesmaa, R., Norman, M., Neve, E.P., Scheynius, A., and Gabrielsson, S. (2007). Exosomes with immune modulatory features are present in human breast milk. J Immunol 179, 1969–1978.CrossRefGoogle Scholar
  2. Agarwal, S., Karmaus, W., Davis, S., and Gangur, V. (2011). Immune markers in breast milk and fetal and maternal body fluids: a systematic review of perinatal concentrations. J Hum Lact 27, 171–186.CrossRefGoogle Scholar
  3. Bandres, E., Bitarte, N., Arias, F., Agorreta, J., Fortes, P., Agirre, X., Zarate, R., Diaz-Gonzalez, J.A., Ramirez, N., Sola, J.J., et al. (2009). microRNA-451 regulates macrophage migration inhibitory factor production and proliferation of gastrointestinal cancer cells. Clin Cancer Res 15, 2281–2290.CrossRefGoogle Scholar
  4. Chen, X., Ba, Y., Ma, L., Cai, X., Yin, Y., Wang, K., Guo, J., Zhang, Y., Chen, J., Guo, X., et al. (2008). Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18, 997–1006.CrossRefGoogle Scholar
  5. Chen, X., Gao, C., Li, H., Huang, L., Sun, Q., Dong, Y., Tian, C., Gao, S., Dong, H., Guan, D., et al. (2010). Identification and characterization of microRNAs in raw milk during different periods of lactation, commercial fluid, and powdered milk products. Cell Res 20, 1128–1137.CrossRefGoogle Scholar
  6. El Gazzar, M., and McCall, C.E. (2012). MicroRNAs regulatory networks in myeloid lineage development and differentiation: regulators of the regulators. Immunol Cell Biol 90, 587–593.CrossRefGoogle Scholar
  7. Fahim, M., Millar, A.A., Wood, C.C., and Larkin, P.J. (2012). Resistance to Wheat streak mosaic virus generated by expression of an artificial polycistronic microRNA in wheat. Plant Biotechnol J 2, 150–163.CrossRefGoogle Scholar
  8. Feng, R., Zhao, C., Li, M., Harrison, T.J., Qiao, Z., Feng, Y., Ma, Z., and Wang, Y. (2011). Infection dynamics of hepatitis E virus in naturally infected pigs in a Chinese farrow-to-finish farm. Infect Genet Evol 11, 1727–1731.CrossRefGoogle Scholar
  9. Hata, T., Murakami, K., Nakatani, H., Yamamoto, Y., Matsuda, T., and Aoki, N. (2010). Isolation of bovine milk-derived microvesicles carrying mRNAs and microRNAs. Biochem Biophys Res Commun 396, 528–533.CrossRefGoogle Scholar
  10. Honorio-Franca, A.C., Carvalho, M.P., Isaac, L., Trabulsi, L.R., and Carneiro-Sampaio, M.M. (1997). Colostral mononuclear phagocytes are able to kill enteropathogenic Escherichia coli opsonized with colostral IgA. Scand J Immunol 46, 59–66.CrossRefGoogle Scholar
  11. Honorio-Franca, A.C., Launay, P., Carneiro-Sampaio, M.M., and Monteiro, R.C. (2001). Colostral neutrophils express Fc alpha receptors (CD89) lacking gamma chain association and mediate noninflammatory properties of secretory IgA. J Leukoc Biol 69, 289–296.Google Scholar
  12. Huang, S., and He, X. (2010). microRNAs: tiny RNA molecules, huge driving forces to move the cell. Protein Cell 1, 916–926.CrossRefGoogle Scholar
  13. Huang, Y., Zou, Q., Song, H., Song, F., Wang, L., Zhang, G., and Shen, X. (2010). A study of miRNAs targets prediction and experimental validation. Protein Cell 1, 979–986.CrossRefGoogle Scholar
  14. Kimura, M., Oh, S., Narabayashi, S., and Taguchi, T. (2012). Usefulness of lymphocyte stimulation test for the diagnosis of intestinal cow’s milk allergy in infants. Int Arch Allergy Immunol 157, 58–64.CrossRefGoogle Scholar
  15. Kosaka, N., Izumi, H., Sekine, K., and Ochiya, T. (2010). microRNA as a new immune-regulatory agent in breast milk. Silence 1, 7.CrossRefGoogle Scholar
  16. Macchiaverni, P., Arslanian, C., Frazao, J.B., Palmeira, P., Russo, M., Verhasselt, V., and Condino-Neto, A. (2011). Mother to child transfer of IgG and IgA antibodies against Dermatophagoides pteronyssinus. Scand J Immunol 6, 619–627.CrossRefGoogle Scholar
  17. Oishi, N., and Wang, X.W. (2011). Novel therapeutic strategies for targeting liver cancer stem cells. Int J Biol Sci 7, 517–535.CrossRefGoogle Scholar
  18. Patiroglu, T., and Kondolot, M. (2011). The effect of bovine colostrum on viral upper respiratory tract infections in children with immunoglobulin A deficiency. Clin Respir J. doi: 10.1111/j.1752-699X.2011.00268.x.Google Scholar
  19. Pigati, L., Yaddanapudi, S.C., Iyengar, R., Kim, D.J., Hearn, S.A., Danforth, D., Hastings, M.L., and Duelli, D.M. (2010). Selective release of microRNA species from normal and malignant mammary epithelial cells. PLoS One 5, e13515.CrossRefGoogle Scholar
  20. Qin, L., Chen, Y., Niu, Y., Chen, W., Wang, Q., Xiao, S., Li, A., Xie, Y., Li, J., Zhao, X., et al. (2010). A deep investigation into the adipogenesis mechanism: profile of microRNAs regulating adipogenesis by modulating the canonical Wnt/beta-catenin signaling pathway. BMC Genomics 11, 320.CrossRefGoogle Scholar
  21. Sharma, A., Kumar, M., Aich, J., Hariharan, M., Brahmachari, S.K., Agrawal, A., and Ghosh, B. (2009). Posttranscriptional regulation of interleukin-10 expression by hsa-miR-106a. Proc Natl Acad Sci U S A 106, 5761–5766.CrossRefGoogle Scholar
  22. Skog, J., Wurdinger, T., van Rijn, S., Meijer, D.H., Gainche, L., Sena-Esteves, M., Curry, W.T., Jr., Carter, B.S., Krichevsky, A.M., and Breakefield, X.O. (2008). Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10, 1470–1476.CrossRefGoogle Scholar
  23. Sonkoly, E., Stahle, M., and Pivarcsi, A. (2008). MicroRNAs and immunity: novel players in the regulation of normal immune function and inflammation. Semin Cancer Biol 18, 131–140.CrossRefGoogle Scholar
  24. Vickers, K.C., Palmisano, B.T., Shoucri, B.M., Shamburek, R.D., and Remaley, A.T. (2011). MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol 13, 423–433.CrossRefGoogle Scholar
  25. Zhang, L., Hou, D., Chen, X., Li, D., Zhu, L., Zhang, Y., Li, J., Bian, Z., Liang, X., Cai, X., et al. (2012). Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA. Cell Res 22, 107–126.CrossRefGoogle Scholar
  26. Zhang, Y., Liu, D., Chen, X., Li, J., Li, L., Bian, Z., Sun, F., Lu, J., Yin, Y., Cai, X., et al. (2010). Secreted monocytic miR-150 enhances targeted endothelial cell migration. Mol Cell 39, 133–144.CrossRefGoogle Scholar
  27. Zhou, Q., Li, M., Wang, X., Li, Q., Wang, T., Zhu, Q., Zhou, X., Wang, X., Gao, X., and Li, X. (2012). Immune-related microRNAs are abundant in breast milk exosomes. Int J Biol Sci 8, 118–123.CrossRefGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical BiotechnologyNanjing University School of Life SciencesNanjingChina
  2. 2.Department of VirologyUniversity of California School of Public HealthBerkeleyUSA

Personalised recommendations