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Reduced immune responses in chimeric mice engrafted with bone marrow cells from mice with airways inflammation

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Abstract

Objective

During respiratory inflammation, it is generally assumed that dendritic cells differentiating from the bone marrow are immunogenic rather than immunoregulatory. Using chimeric mice, the outcomes of airways inflammation on bone marrow progenitor cells were studied.

Methods

Immune responses were analyzed in chimeric mice engrafted for >16 weeks with bone marrow cells from mice with experimental allergic airways disease (EAAD).

Results

Responses to sensitization and challenge with the allergen causing inflammation in the bone marrow-donor mice were significantly reduced in the chimeric mice engrafted with bone marrow cells from mice with EAAD (EAAD-chimeric). Responses to intranasal LPS and topical fluorescein isothiocyanate (non-specific challenges) were significantly attenuated. Fewer activated dendritic cells from the airways and skin of the EAAD-chimeric mice could be tracked to the draining lymph nodes, and may contribute to the significantly reduced antigen/chemical-induced hypertrophy in the draining nodes, and the reduced immune responses to sensitizing allergens. Dendritic cells differentiating in vitro from the bone marrow of >16 weeks reconstituted EAAD-chimeric mice retained an ability to poorly prime immune responses when transferred into naïve mice.

Conclusions

Dendritic cells developing from bone marrow progenitors during airways inflammation are altered such that daughter cells have reduced antigen priming capabilities.

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Abbreviations

ADLN:

Airway-draining lymph nodes

BALF:

Bronchoalveolar lavage fluid

BM:

Bone marrow

DC:

Dendritic cell

DNBS:

Dinitrobenzene sulfonic acid sodium salt

DNFB:

2,4-dinitro-1-fluorobenzene

EAAD:

Experimental allergic airways disease

FITC:

Fluorescein isothiocyanate

FLT3-L:

Fms-like tyrosine kinase 3-Ligand

GM-CSF:

Granulocyte-macrophage colony stimulating factor

OVA:

Ovalbumin

PGE2 :

Prostaglandin E2

SDLN:

Skin-draining lymph nodes

References

  1. Takizawa H, Boettcher S, Manz MG. Demand-adapted regulation of early hematopoiesis in infection and inflammation. Blood. 2012;119:2991–3002.

    Article  CAS  PubMed  Google Scholar 

  2. King KY, Goodell MA. Inflammatory modulation of HSCs: viewing the HSC as a foundation for the immune response. Nat Rev Immunol. 2011;11:685–92.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Baldridge MT, King KY, Boles NC, Weksberg DC, Goodell MA. Quiescent haematopoietic stem cells are activated by IFN-γ in response to chronic infection. Nature. 2010;465:793–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Esplin BL, Shimazu T, Welner RS, Garrett KP, Nie L, Zhang Q, et al. Chronic exposure to a TLR ligand injures hematopoietic stem cells. J Immunol. 2011;186:5367–75.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Liu K, Nussenzweig MC. Origin and development of dendritic cells. Immunol Rev. 2010;234:45–54.

    Article  CAS  PubMed  Google Scholar 

  6. Kushwah R, Hu J. Complexity of dendritic cell subsets and their function in the host immune system. Immunology. 2011;133:409–19.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Scott NM, Ng RLX, Strickland DH, Bisley JL, Bazely SA, Gorman S, et al. Toward homeostasis: regulatory dendritic cells from the bone marrow of mice with inflammation of the airways and peritoneal cavity. Am J Pathol. 2012;181:535–47.

    Article  CAS  PubMed  Google Scholar 

  8. Ng RLX, Bisley JL, Gorman S, Norval M, Hart PH. Ultraviolet irradiation of mice reduces the competency of bone marrow-derived CD11c+ cells via an indomethacin-inhibitable pathway. J Immunol. 2010;185:7207–15.

    Article  CAS  PubMed  Google Scholar 

  9. McGlade JP, Gorman S, Zosky GR, Larcombe AN, Sly PD, Finlay-Jones JJ, et al. Suppression of the asthmatic phenotype by UVB-induced, antigen-specific regulatory cells. Clin Exp Allergy. 2007;37:1267–76.

    Article  CAS  PubMed  Google Scholar 

  10. Kalinski P. Regulation of immune responses by prostaglandin E2. J Immunol. 2012;188:21–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Hoggatt J, Singh P, Sampath J, Pelus LM. Prostaglandin E2 enhances hematopoietic stem cell homing, survival and proliferation. Blood. 2009;113:5444–55.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Ng RLX, Scott NM, Strickland DH, Gorman S, Grimbaldeston MA, Norval M, et al. Altered immunity and dendritic cell activity in the periphery of mice after long-term engraftment with bone marrow from UV-irradiated mice. J Immunol. 2013;190:5471–84.

    Article  CAS  PubMed  Google Scholar 

  13. Scott NM, Lambert MJM, Gorman S, McGlade JP, Hart PH. Differences in control by UV radiation of inflammatory airways disease in naïve and allergen pre-sensitised mice. Photochem Photobiol Sci. 2011;10:894–901.

    Article  Google Scholar 

  14. Coquerelle C, Moser M. DC subsets in positive and negative regulation of immunity. Immunol Rev. 2010;234:317–34.

    Article  CAS  PubMed  Google Scholar 

  15. Merad M, Manz MG, Karsunky H, Wagers A, Peters W, Charo I, et al. Langerhans cells renew in the skin throughout life under steady-state conditions. Nat Immunol. 2002;3:1135–41.

    Article  CAS  PubMed  Google Scholar 

  16. Ng RLX, Scott NM, Bisley J, Lambert MLM, Gorman S, Norval M, et al. Characterisation of regulatory dendritic cells differentiated from the bone marrow of UV-irradiated mice. Immunology. 2013;140:399–412.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Juttermann R, Li E, Jaenisch R. Toxicity of 5-aza-2′-deoxycytidine to mammalian cells is mediated primarily by covalent trapping of DNA methyltransferase rather than DNA demethylation. Proc Natl Acad Sci USA. 1994;91:11797–801.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Jordan CT, Lemischka IR. Clonal and systemic analysis of long-term hematopoiesis in the mouse. Genes Dev. 1990;4:220–32.

    Article  CAS  PubMed  Google Scholar 

  19. Frisch BJ, Porter RL, Gigliotti BJ, Olm-Shipman AJ, Weber JM, O’Keefe RJ, et al. In vivo prostaglandin E2 treatment alters the bone marrow microenvironment and preferentially expands short-term hematopoietic stem cells. Blood. 2009;114:4054–63.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Netea MG. Training innate immunity: the changing concept of immunological memory in innate host defence. Eur J Clin Invest. 2013;43:881–4.

    Article  CAS  PubMed  Google Scholar 

  21. Yanez A, Hassanzadeh-Kiabi N, Ng MY, Megias J, Subramanian A, Liu GY, et al. Detection of a TLR2 agonist by hematopoietic stem and progenitor cells impacts the function of the macrophages they produce. Eur J Immunol. 2013;43:2526–33.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Kamath AT, Pooley J, O’Keeffe MA, Vremec D, Zhan Y, Lew AM, et al. The development, maturation, and turnover rate of mouse spleen dendritic cell populations. J Immunol. 2000;165:6762–70.

    Article  CAS  PubMed  Google Scholar 

  23. Kamath AT, Henri S, Battye F, Tough DF, Shortman K. Developmental kinetics and lifespan of dendritic cells in mouse lymphoid organs. Blood. 2002;100:1734–41.

    CAS  PubMed  Google Scholar 

  24. Wu L, Liu YJ. Development of dendritic-cell lineages. Immunity. 2007;26:741–50.

    Article  CAS  PubMed  Google Scholar 

  25. Holt PG, Sly PD. Viral infections and atopy in asthma pathogenesis: new rationales for asthma prevention and treatment. Nat Med. 2012;18:726–35.

    Article  CAS  PubMed  Google Scholar 

  26. Scott NM, Ng RLX, Gorman S, Norval M, Waithman J, Hart PH. Prostaglandin E2 imprints a long-lasting effect on dendritic cell progenitors in the bone marrow. J Leuk Biol. 2014;95:225–32.

    Article  Google Scholar 

  27. Moore ML, Peebles RS. Update on the role of prostaglandins in allergic lung inflammation: separating friends from foes, harder than you think. J Allergy Clin Immunol. 2006;117:1036–9.

    Article  CAS  PubMed  Google Scholar 

  28. Peebles RS, Hashimoto K, Morrow JD, Dworski R, Collins RD, Hashimoto Y, et al. Selective cyclooxygenase-1 and -2 inhibitors each increase allergic inflammation and airway hyperresponsiveness in mice. Am J Respir Crit Care Med. 2002;165:1154–60.

    Article  PubMed  Google Scholar 

  29. Li H, Edin ML, Bradbury JA, Graves JP, DeGraff LM, Gruzdev A, et al. Cyclooxygenase-2 inhibits T helper cell type 9 differentiation during allergic lung inflammation via down-regulation of IL-17RB. Am J Respir Crit Care Med. 2013;187:812–22.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Pelus LM, Hoggatt J. Pleiotropic effects of prostaglandin E2 in hematopoiesis; prostaglandin E2 and other eicosanoids regulate hematopoietic stem and progenitor cell function. Prostaglandins Other Lipid Mediat. 2011;96:3–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Porter RL, Georger MA, Bromberg O, McGrath KE, Frisch BJ, Becker MW, et al. Prostaglandin E2 increases hematopoietic stem cell survival and accelerates hematopoietic recovery after radiation injury. Stem Cells. 2013;31:372–83.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Ikushima YM, Arai F, Hosokawa K, Toyama H, Takubo K, Furuyashiki T, et al. Prostaglandin E2 regulates murine hematopoietic stem/progenitor cells directly via EP4 receptor and indirectly through mesenchymal progenitor cells. Blood. 2013;121:1995–2007.

    Article  CAS  PubMed  Google Scholar 

  33. Hoggatt J, Mohammad KS, Singh P, Hoggatt AF, Chitteti BR, Speth JM, et al. Differential stem- and progenitor-cell trafficking by prostaglandin E2. Nature. 2013;495:365–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Xia D, Wang D, Kim SH, Katoh H, DuBois RN. Prostaglandin E2 promotes intestinal tumor growth via DNA methylation. Nat Med. 2012;18:224–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Wahlestedt M, Norddahl GL, Sten G, Ugale A, Frisk MM, Mattsson R, et al. An epigenetic component of hematopoietic stem cell aging amenable to reprogramming into a young state. Blood. 2013;121:4257–64.

    Article  CAS  PubMed  Google Scholar 

  36. Eisenbarth SC, Williams A, Colegio OR, Meng H, Strowig T, Rongvaux A, et al. NLRP10 is a NOD-like receptor essential to initiate adaptive immunity by dendritic cells. Nature. 2012;484:510–3.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Gartlan KH, Wee JL, Demaria MC, Nastovska R, Chang TM, Jones EL, et al. Tetraspanin CD37 contributes to the initiation of cellular immunity by promoting dendritic cell migration. Eur J Immunol. 2013;43:1208–19.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank the Asthma Foundation WA and the National Health and Medical Research Council of Australia for funding this study.

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Authors and Affiliations

  1. Telethon Kids Institute, University of Western Australia, PO Box 855, West Perth, WA, 6872, Australia

    Naomi M. Scott, Royce L. X. Ng, Terence A. McGonigle, Shelley Gorman & Prue H. Hart

Authors
  1. Naomi M. Scott
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  2. Royce L. X. Ng
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  3. Terence A. McGonigle
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  4. Shelley Gorman
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  5. Prue H. Hart
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Corresponding author

Correspondence to Prue H. Hart.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the Telethon Kids Institute, University of Western Australia, at which the studies were conducted (Approval Number 235). This article does not contain any studies with human participants performed by any of the authors.

Funding

The Asthma Foundation WA and the National Health and Medical Research Council of Australia (572660).

Additional information

Responsible Editor: Artur Bauhofer.

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Scott, N.M., Ng, R.L.X., McGonigle, T.A. et al. Reduced immune responses in chimeric mice engrafted with bone marrow cells from mice with airways inflammation. Inflamm. Res. 64, 861–873 (2015). https://doi.org/10.1007/s00011-015-0868-z

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  • DOI: https://doi.org/10.1007/s00011-015-0868-z

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