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Polymeric IgA1 controls erythroblast proliferation and accelerates erythropoiesis recovery in anemia

Nature Medicine volume 17, pages 1456–1465 (2011)Cite this article

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Abstract

Anemia because of insufficient production of and/or response to erythropoietin (Epo) is a major complication of chronic kidney disease and cancer. The mechanisms modulating the sensitivity of erythroblasts to Epo remain poorly understood. We show that, when cultured with Epo at suboptimal concentrations, the growth and clonogenic potential of erythroblasts was rescued by transferrin receptor 1 (TfR1)-bound polymeric IgA1 (pIgA1). Under homeostatic conditions, erythroblast numbers were increased in mice expressing human IgA1 compared to control mice. Hypoxic stress of these mice led to increased amounts of pIgA1 and erythroblast expansion. Expression of human IgA1 or treatment of wild-type mice with the TfR1 ligands pIgA1 or iron-loaded transferrin (Fe-Tf) accelerated recovery from acute anemia. TfR1 engagement by either pIgA1 or Fe-Tf increased cell sensitivity to Epo by inducing activation of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways. These cellular responses were mediated through the TfR1-internalization motif, YXXΦ. Our results show that pIgA1 and TfR1 are positive regulators of erythropoiesis in both physiological and pathological situations. Targeting this pathway may provide alternate approaches to the treatment of ineffective erythropoiesis and anemia.

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Figure 1: pIgA1 binds erythroblasts and enhances their growth.
Figure 2: Enhanced erythropoiesis induced by hypoxic stress in α1KI mice.
Figure 3: Accelerated recovery from acute anemia by TfR1 ligands.
Figure 4: Noncompetitive binding to TfR1 and convergent function of Fe-Tf and pIgA1.
Figure 5: TfR1 is a signaling-competent molecule.
Figure 6: TfR1 triggering potentiates and sensitizes Epo signaling.

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References

  1. Russell, E.S. Hereditary anemias of the mouse: a review for geneticists. Adv. Genet. 20, 357–459 (1979).

    Article  CAS  PubMed  Google Scholar 

  2. Goldwasser, E. Erythropoietin and its mode of action. Blood Cells 10, 147–162 (1984).

    CAS  PubMed  Google Scholar 

  3. Zermati, Y. et al. Caspase activation is required for terminal erythroid differentiation. J. Exp. Med. 193, 247–254 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ribeil, J.A. et al. Hsp70 regulates erythropoiesis by preventing caspase-3-mediated cleavage of GATA-1. Nature 445, 102–105 (2007).

    Article  CAS  PubMed  Google Scholar 

  5. Koury, M.J. & Bondurant, M.C. Erythropoietin retards DNA breakdown and prevents programmed death in erythroid progenitor cells. Science 248, 378–381 (1990).

    Article  CAS  PubMed  Google Scholar 

  6. Kelley, L.L. et al. Survival or death of individual proerythroblasts results from differing erythropoietin sensitivities: a mechanism for controlled rates of erythrocyte production. Blood 82, 2340–2352 (1993).

    CAS  PubMed  Google Scholar 

  7. Levy, J.E., Jin, O., Fujiwara, Y., Kuo, F. & Andrews, N.C. Transferrin receptor is necessary for development of erythrocytes and the nervous system. Nat. Genet. 21, 396–399 (1999).

    Article  CAS  PubMed  Google Scholar 

  8. Lebrón, J.A. et al. Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor. Cell 93, 111–123 (1998).

    Article  PubMed  Google Scholar 

  9. Radoshitzky, S.R. et al. Transferrin receptor 1 is a cellular receptor for New World haemorrhagic fever arenaviruses. Nature 446, 92–96 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Schmidt, P.J., Toran, P.T., Giannetti, A.M., Bjorkman, P.J. & Andrews, N.C. The transferrin receptor modulates Hfe-dependent regulation of hepcidin expression. Cell Metab. 7, 205–214 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Moura, I.C. et al. Identification of the transferrin receptor as a novel immunoglobulin (Ig)A1 receptor and its enhanced expression on mesangial cells in IgA nephropathy. J. Exp. Med. 194, 417–425 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Matysiak-Budnik, T. et al. Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease. J. Exp. Med. 205, 143–154 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Woof, J.M. & Mestecky, J. Mucosal immunoglobulins. Immunol. Rev. 206, 64–82 (2005).

    Article  CAS  PubMed  Google Scholar 

  14. Monteiro, R.C. & Van De Winkel, J.G. IgA Fc receptors. Annu. Rev. Immunol. 21, 177–204 (2003).

    Article  CAS  PubMed  Google Scholar 

  15. Moura, I.C. et al. A neutralizing monoclonal antibody (mAb A24) directed against the transferrin receptor induces apoptosis of tumor T lymphocytes from ATL patients. Blood 103, 1838–1845 (2004).

    Article  CAS  PubMed  Google Scholar 

  16. Jacob, C.M., Pastorino, A.C., Fahl, K., Carneiro-Sampaio, M. & Monteiro, R.C. Autoimmunity in IgA deficiency: revisiting the role of IgA as a silent housekeeper. J. Clin. Immunol. 28 (Suppl 1), S56–S61 (2008).

    Article  CAS  PubMed  Google Scholar 

  17. Moura, I.C. et al. Glycosylation and size of IgA1 are essential for interaction with mesangial transferrin receptor in IgA nephropathy. J. Am. Soc. Nephrol. 15, 622–634 (2004).

    Article  CAS  PubMed  Google Scholar 

  18. Duchez, S. et al. Premature replacement of mu with alpha immunoglobulin chains impairs lymphopoiesis and mucosal homing but promotes plasma cell maturation. Proc. Natl. Acad. Sci. USA 107, 3064–3069 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Erlandsson, L. et al. Joining chain-expressing and -nonexpressing B cell populations in the mouse. J. Exp. Med. 194, 557–570 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Mestecky, J., Lue, C. & Russell, M.W. Selective transport of IgA. Cellular and molecular aspects. Gastroenterol. Clin. North Am. 20, 441–471 (1991).

    CAS  PubMed  Google Scholar 

  21. De Maria, R. et al. Apoptotic role of Fas/Fas ligand system in the regulation of erythropoiesis. Blood 93, 796–803 (1999).

    CAS  PubMed  Google Scholar 

  22. Suzuki, M. et al. Real-time monitoring of stress erythropoiesis in vivo using Gata1 and β-globin LCR luciferase transgenic mice. Blood 108, 726–733 (2006).

    Article  CAS  PubMed  Google Scholar 

  23. Koury, M.J. Erythropoietin: the story of hypoxia and a finely regulated hematopoietic hormone. Exp. Hematol. 33, 1263–1270 (2005).

    Article  CAS  PubMed  Google Scholar 

  24. Bozzini, C.E. et al. The biology of stress erythropoiesis and erythropoietin production. Ann. N. Y. Acad. Sci. 718, 83–(1994).

    Article  Google Scholar 

  25. Socolovsky, M. Molecular insights into stress erythropoiesis. Curr. Opin. Hematol. 14, 215–224 (2007).

    Article  PubMed  Google Scholar 

  26. Fossati-Jimack, L. et al. High pathogenic potential of low-affinity autoantibodies in experimental autoimmune hemolytic anemia. J. Exp. Med. 190, 1689–1696 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Rifai, A., Fadden, K., Morrison, S.L. & Chintalacharuvu, K.R. The N-glycans determine the differential blood clearance and hepatic uptake of human immunoglobulin (Ig)A1 and IgA2 isotypes. J. Exp. Med. 191, 2171–2182 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Li, H. et al. Transferrin therapy ameliorates disease in β-thalassemic mice. Nat. Med. 16, 177–182 (2010).

    Article  CAS  PubMed  Google Scholar 

  29. Callens, C. et al. Targeting iron homeostasis induces cellular differentiation and synergizes with differentiating agents in acute myeloid leukemia. J. Exp. Med. 207, 731–750 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Moura, I.C. et al. Engagement of transferrin receptor by polymeric IgA1: evidence for a positive feedback loop involving increased receptor expression and mesangial cell proliferation in IgA nephropathy. J. Am. Soc. Nephrol. 16, 2667–2676 (2005).

    Article  CAS  PubMed  Google Scholar 

  31. Lev, S., Yarden, Y. & Givol, D. Dimerization and activation of the kit receptor by monovalent and bivalent binding of the stem cell factor. J. Biol. Chem. 267, 15970–15977 (1992).

    CAS  PubMed  Google Scholar 

  32. Lev, S., Yarden, Y. & Givol, D. A recombinant ectodomain of the receptor for the stem cell factor (SCF) retains ligand-induced receptor dimerization and antagonizes SCF-stimulated cellular responses. J. Biol. Chem. 267, 10866–10873 (1992).

    CAS  PubMed  Google Scholar 

  33. Miller, B.A. et al. Identification of the erythropoietin receptor domain required for calcium channel activation. J. Biol. Chem. 274, 20465–20472 (1999).

    Article  CAS  PubMed  Google Scholar 

  34. Collawn, J.F. et al. Transferrin receptor internalization sequence YXRF implicates a tight turn as the structural recognition motif for endocytosis. Cell 63, 1061–1072 (1990).

    Article  CAS  PubMed  Google Scholar 

  35. Hirschler-Laszkiewicz, I. et al. TRPC3 activation by erythropoietin is modulated by TRPC6. J. Biol. Chem. 284, 4567–4581 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Johnson, M.B. & Enns, C.A. Diferric transferrin regulates transferrin receptor 2 protein stability. Blood 104, 4287–4293 (2004).

    Article  CAS  PubMed  Google Scholar 

  37. Huebers, H.A., Josephson, B., Huebers, E., Csiba, E. & Finch, C.A. Occupancy of the iron binding sites of human transferrin. Proc. Natl. Acad. Sci. USA 81, 4326–4330 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Richardson, D.R. & Ponka, P. The molecular mechanisms of the metabolism and transport of iron in normal and neoplastic cells. Biochim. Biophys. Acta 1331, 1–40 (1997).

    Article  CAS  PubMed  Google Scholar 

  39. Chan, R.Y., Ponka, P. & Schulman, H.M. Transferrin-receptor–independent but iron-dependent proliferation of variant Chinese hamster ovary cells. Exp. Cell Res. 202, 326–336 (1992).

    Article  CAS  PubMed  Google Scholar 

  40. Gutiérrez, L. et al. Ablation of Gata1 in adult mice results in aplastic crisis, revealing its essential role in steady-state and stress erythropoiesis. Blood 111, 4375–4385 (2008).

    Article  PubMed  Google Scholar 

  41. Li, K., Menon, M.P., Karur, V.G., Hegde, S. & Wojchowski, D.M. Attenuated signaling by a phosphotyrosine-null Epo receptor form in primary erythroid progenitor cells. Blood 102, 3147–3153 (2003).

    Article  CAS  PubMed  Google Scholar 

  42. Arcasoy, M.O. & Jiang, X. Co-operative signalling mechanisms required for erythroid precursor expansion in response to Epo and stem cell factor. Br. J. Haematol. 130, 121–129 (2005).

    Article  CAS  PubMed  Google Scholar 

  43. Perry, J.M., Harandi, O.F. & Paulson, R.F. BMP4, SCF, and hypoxia cooperatively regulate the expansion of murine stress erythroid progenitors. Blood 109, 4494–4502 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Menon, M.P. et al. Signals for stress erythropoiesis are integrated via an erythropoietin receptor-phosphotyrosine-343-Stat5 axis. J. Clin. Invest. 116, 683–694 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Harandi, O.F., Hedge, S., Wu, D.C., McKeone, D. & Paulson, R.F. Murine erythroid short-term radioprotection requires a BMP4-dependent, self-renewing population of stress erythroid progenitors. J. Clin. Invest. 120, 4507–4519 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Auerbach, M. et al. Intravenous iron optimizes the response to recombinant human erythropoietin in cancer patients with chemotherapy-related anemia: a multicenter, open-label, randomized trial. J. Clin. Oncol. 22, 1301–1307 (2004).

    Article  CAS  PubMed  Google Scholar 

  47. Besarab, A. & Coyne, D.W. Iron supplementation to treat anemia in patients with chronic kidney disease. Nat. Rev. Nephrol. 6, 699–710 (2010).

    Article  CAS  PubMed  Google Scholar 

  48. Cook, J.D., Finch, C.A. & Smith, N.J. Evaluation of the iron status of a population. Blood 48, 449–455 (1976).

    CAS  PubMed  Google Scholar 

  49. Keel, S.B. & Abkowitz, J.L. The microcytic red cell and the anemia of inflammation. N. Engl. J. Med. 361, 1904–1906 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Means, R.T. Jr. & Krantz, S.B. Progress in understanding the pathogenesis of the anemia of chronic disease. Blood 80, 1639–1647 (1992).

    PubMed  Google Scholar 

  51. Zoller, E.E. et al. Hemophagocytosis causes a consumptive anemia of inflammation. J. Exp. Med. 208, 1203–1214 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Pasquier, B. et al. Identification of FcαRI as an inhibitory receptor that controls inflammation: dual role of FcRγ ITAM. Immunity 22, 31–42 (2005).

    CAS  PubMed  Google Scholar 

  53. Kerr, M.A. The structure and function of human IgA. Biochem. J. 271, 285–296 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Meehan, R. et al. Operation Everest II: alterations in the immune system at high altitudes. J. Clin. Immunol. 8, 397–406 (1988).

    Article  CAS  PubMed  Google Scholar 

  55. Bauer, A. et al. The glucocorticoid receptor is required for stress erythropoiesis. Genes Dev. 13, 2996–3002 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Broudy, V.C., Lin, N.L., Priestley, G.V., Nocka, K. & Wolf, N.S. Interaction of stem cell factor and its receptor c-kit mediates lodgment and acute expansion of hematopoietic cells in the murine spleen. Blood 88, 75–81 (1996).

    CAS  PubMed  Google Scholar 

  57. Lenox, L.E., Perry, J.M. & Paulson, R.F. BMP4 and Madh5 regulate the erythroid response to acute anemia. Blood 105, 2741–2748 (2005).

    Article  CAS  PubMed  Google Scholar 

  58. Falanga, V. et al. Hypoxia upregulates the synthesis of TGF-β 1 by human dermal fibroblasts. J. Invest. Dermatol. 97, 634–637 (1991).

    Article  CAS  PubMed  Google Scholar 

  59. Dullaers, M. et al. A T cell-dependent mechanism for the induction of human mucosal homing immunoglobulin A-secreting plasmablasts. Immunity 30, 120–129 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Liu, Y. et al. Suppression of Fas-FasL coexpression by erythropoietin mediates erythroblast expansion during the erythropoietic stress response in vivo. Blood 108, 123–133 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by Agence Nationale pour la Recherche, Institut National contre le Cancer, cancéropôle d'Ile de France, Fondation pour la Recherche Médicale, Fondation de France, Association Laurette Fugain, Association pour la Recherche contre le Cancer, Société Française d'Hématologie, cent pour sang la vie, la Ligue contre le Cancer and INSERM/PNRNU2007 grants. S.C. is a recipient of Fondation pour la Recherche Médicale grant and a Société Française d'Hématologie grant. We would like to thank J. Kersual and S. Dauzet (CNRS UMR-S 8147) for experimental help and the Departments of Hematology, Obstetrics and Otorhinolaryngology at the Necker Hospital (Paris, France) for providing blood samples, cord blood samples and tonsil samples, respectively. We would like to thank J.L. Danan (CNRS FRE 3210), M. Heinis (INSERM U845), B. Ruiz (INSERM U780) (located at Paris Descartes University, Paris, France) and C. Clerici (INSERM U773, Bichat Hospital, Paris, France) for providing the hypoxia chambers and L.-J. Couderc at the Foch Hospital (Suresnes, France) for providing blood samples. We are especially thankful to S. Izui (Department of Pathology and Immunology, University Medical Center, Geneva, Switzerland) for providing the 34-3C IgG2a monoclonal antibody and for fruitful discussions.

Author information

Author notes

  1. Séverine Coulon & Jean-Antoine Ribeil

    Present address: Present addresses: Service de Pharmacie, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France (S.C.) and Departement de Biothérapie, Hôpital Necker, Paris, France (J.-A.R.).,

  2. Séverine Coulon and Michaël Dussiot: These authors contributed equally to this work.

Authors and Affiliations

  1. Centre National de la Recherche Scientifique (CNRS) Unité Mixte Recherche (UMR) 8147, Université Paris Descartes, Faculté de Médecine, Hôpital Necker, Paris, France

    Séverine Coulon, Michaël Dussiot, Damien Grapton, Celine Callens, Aurelie Fricot, Julie Vandekerckhove, Yael Zermati, Jean-Antoine Ribeil, Geneviève Courtois & Olivier Hermine

  2. Institut National de la Santé et de la Recherche Médicale (INSERM) U699, Paris, France

    Michaël Dussiot, Damien Grapton, Thiago Trovati Maciel, Pamella Huey Mei Wang, Meetu Kaushik Tiwari, Saurabh Agarwal, Houda Tamouza, Marc Benhamou, Renato C Monteiro & Ivan C Moura

  3. Faculté de Médecine and Université Denis Diderot Paris VII, Paris, France

    Michaël Dussiot, Damien Grapton, Thiago Trovati Maciel, Pamella Huey Mei Wang, Meetu Kaushik Tiwari, Saurabh Agarwal, Houda Tamouza, Marc Benhamou, Renato C Monteiro & Ivan C Moura

  4. Clinique Geoffroy Saint-Hilaire, Paris, France

    Kamel Djedaini

  5. Université de Limoges, CNRS UMR 6101, Limoges, France

    Zeliha Oruc, Virginie Pascal & Michel Cogné

  6. Service d'Immuno-Hématologie, Faculté de Médecine and Université Denis Diderot Paris VII, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Louis, Paris, France

    Bertrand Arnulf

  7. Laboratoire EA3963, Faculté de Médecine and Université Denis Diderot Paris VII, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Louis, Paris, France

    Bertrand Arnulf

  8. INSERM U1013, Université Paris Descartes, Faculté de Médecine, Hôpital Necker, Paris, France

    Marie-Alexandra Alyanakian

  9. Laboratoire d'Immunologie Biologique, Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Paris, France

    Marie-Alexandra Alyanakian

  10. Département d'Hématologie, Institut Cochin, Paris, France

    Patrick Mayeux

  11. INSERM U567, Paris, France

    Patrick Mayeux

  12. CNRS UMR 8104, Université Paris Descartes, Faculté de Médecine, Paris, France

    Patrick Mayeux

  13. Immunology Group, Lund University, Lund, Sweden

    Tomas Leanderson

  14. Service d'Hématologie clinique, Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Paris, France

    Olivier Hermine

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  1. Séverine Coulon
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Contributions

S.C., M.D. and D.G. designed and performed all experiments, analyzed the data and helped write the manuscript. T.T.M. performed calcium experiments, analyzed the data and helped write the manuscript. P.H.M.W., C.C., A.F., J.V., H.T., Y.Z. and G.C. performed experiments and analyzed the data. M.K.T. planned, designed and constructed the TfR1 mutants and helped to write the manuscript. S.A. performed molecular biology experiments. J.-A.R., K.D., Z.O., V.P., B.A., M.-A.A., T.L. and M.C. provided human samples and mice. P.M. contributed to writing the manuscript and provided helpful discussions. M.B. provided helpful discussions and crucial analysis of the data and wrote the manuscript. R.C.M. supervised the project, analyzed the data and wrote the manuscript. O.H. designed the study, supervised the overall project, analyzed the data and wrote the manuscript. I.C.M. designed the study, supervised the overall project, performed experiments, analyzed the data and wrote the manuscript.

Corresponding authors

Correspondence to Renato C Monteiro, Olivier Hermine or Ivan C Moura.

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The authors declare no competing financial interests.

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Coulon, S., Dussiot, M., Grapton, D. et al. Polymeric IgA1 controls erythroblast proliferation and accelerates erythropoiesis recovery in anemia. Nat Med 17, 1456–1465 (2011). https://doi.org/10.1038/nm.2462

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