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Autoimmunity's collateral damage: Gut microbiota strikes 'back'

Nature Medicine volume 17, pages 1055–1056 (2011)Cite this article

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The bacteria resident in the intestine of mammals have coevolved with their hosts and represent an important and highly selected metagenome1 that contributes in numerous ways to the hosts' health2. These commensal bacteria provide defense against pathogenic bacteria not simply by competing for nutrients and physical niches but by inducing specific immune responses. Indeed, the development of the mucosal immune system is dependent on bacteria. Gut microbiota influence the balance between T helper type 1 (TH1) and TH2 lymphocytes3 important in host defense, as well as the development of TH17 cells, which have recently been described to be important in antifungal responses and autoimmune pathology. TH17 cells are absent in the lamina propria of germ-free mice, and colonization of these mice with one bacterial strain, segmented filamentous bacteria (SFB), is sufficient for their reconstitution4.

The consequences of this dependency of TH17 cells on intestinal bacterial flora have recently been highlighted by Wu et al.5, who show that commensal microbes can have profound effects on clinical disease. SFB promote the development of arthritis in the K/BxN mouse model, with disease being abrogated under germ-free conditions and restored after colonization with these bacteria. These mice, which express a transgenic T cell receptor recognizing peptides derived from glucose phosphate isomerase (GPI), develop an arthritis that depends on formation of antibodies to GPI. In germ-free mice, levels of these antibodies are reduced and arthritis is attenuated; however, transfer of the mice into a conventional animal facility restores antibody formation. IL-17 is crucial in this process through its ability to enhance germinal center formation by acting on B lymphocytes expressing IL-17 receptor. Notably, TH17 development can be abrogated when mice are treated with antibiotics targeting Gram-positive bacteria, such as SFB, but not Gram-negative organisms, and this also inhibits arthritis. Manipulation of a single commensal bacterial species can therefore result in potent alterations in systemic rheumatic pathology.

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Figure 1: Commensal bacteria may have a role in producing inflammatory cytokines that can worsen autoimmune disease in the joints.

Katie Vicari

References

  1. Ley, R.E., Peterson, D.A. & Gordon, J.I. Cell 124, 837–848 (2006).

    Article  CAS  PubMed  Google Scholar 

  2. Mazmanian, S.K. & Kasper, D.L. Nat. Rev. Immunol. 6, 849–858 (2006).

    Article  CAS  PubMed  Google Scholar 

  3. Mazmanian, S.K., Liu, C.H., Tzianabos, A.O. & Kasper, D.L. Cell 122, 107–118 (2005).

    Article  CAS  PubMed  Google Scholar 

  4. Ivanov, I.I. et al. Cell 139, 485–498 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Wu, H.J. et al. Immunity 32, 815–827 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Mielants, H. et al. J. Rheumatol. 22, 2273–2278 (1995).

    CAS  PubMed  Google Scholar 

  7. Becker, C. et al. J. Clin. Invest. 112, 693–706 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ciccia, F. et al. Arthritis Rheum. 60, 955–965 (2009).

    Article  CAS  PubMed  Google Scholar 

  9. Burnet, F.M. The Clonal Selection Theory of Acquired Immunity. (Vanderbilt University Press, Nashville, Tennessee, USA, 1959).

    Book  Google Scholar 

  10. McGonagle, D. et al. Arthritis Rheum. 41, 694–700 (1998).

    Article  CAS  PubMed  Google Scholar 

  11. Colbert, R.A., DeLay, M.L., Klenk, E.I. & Layh-Schmitt, G. Immunol. Rev. 233, 181–202 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Goodall, J.C. et al. Proc. Natl. Acad. Sci. USA 107, 17698–17703 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Di Meglio, P. et al. PLoS ONE 6, e17160 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Burton, P.R. et al. Nat. Genet. 39, 1329–1337 (2007).

    Article  CAS  PubMed  Google Scholar 

  15. Qin, J. et al. Nature 464, 59–65 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cua, D.J. & Tato, C.M. Nat. Rev. Immunol. 10, 479–489 (2010).

    Article  CAS  PubMed  Google Scholar 

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  1. Daniel J. Cua and Jonathan P. Sherlock are at Merck Research Laboratories, Palo Alto, California.,

    Daniel J Cua & Jonathan P Sherlock

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Correspondence to Daniel J Cua or Jonathan P Sherlock.

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Cua, D., Sherlock, J. Autoimmunity's collateral damage: Gut microbiota strikes 'back'. Nat Med 17, 1055–1056 (2011). https://doi.org/10.1038/nm0911-1055

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