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PMID: 24332033 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Thymic stromal lymphopoietin-mediated extramedullary hematopoiesis promotes allergic inflammation.

Immunity ·Vol. 39 ·No. 6 ·2013-12-12 ·Pages 1158-70

Siracusa MC, Saenz SA, Wojno ED, Kim BS, Osborne LC, Ziegler CG, Benitez AJ, Ruymann KR, Farber DL, Sleiman PM, Hakonarson H, Cianferoni A, Wang ML, Spergel JM, Comeau MR, Artis D

Abstract

Extramedullary hematopoiesis (EMH) refers to the differentiation of hematopoietic stem cells (HSCs) into effector cells that occurs in compartments outside of the bone marrow. Previous studies linked pattern-recognition receptor (PRR)-expressing HSCs, EMH, and immune responses to microbial stimuli. However, whether EMH operates in broader immune contexts remains unknown. Here, we demonstrate a previously unrecognized role for thymic stromal lymphopoietin (TSLP) in promoting the population expansion of progenitor cells in the periphery and identify that TSLP-elicited progenitors differentiated into effector cells including macrophages, dendritic cells, and granulocytes and that these cells contributed to type 2 cytokine responses. The frequency of circulating progenitor cells was also increased in allergic patients with a gain-of-function polymorphism in TSLP, suggesting the TSLP-EMH pathway might operate in human disease. These data identify that TSLP-induced EMH contributes to the development of allergic inflammation and indicate that EMH is a conserved mechanism of innate immunity.

MeSH Terms
Animals Cytokines/genetics,immunology,metabolism Disease Models, Animal Flow Cytometry Gene Expression Profiling Hematopoiesis, Extramedullary/immunology Humans Hypersensitivity/immunology Inflammation Mice Mice, Inbred C57BL Polymorphism, Genetic Precursor Cells, B-Lymphoid/cytology Spleen/cytology,immunology Trichinellosis/immunology
Chemicals
Cytokines thymic stromal lymphopoietin
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Siracusa Mark C
Department of Microbiology, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Saenz Steven A
Department of Microbiology, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Wojno Elia D Tait
Department of Microbiology, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Kim Brian S
Department of Microbiology, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Osborne Lisa C
Department of Microbiology, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ziegler Carly G
Department of Microbiology, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Benitez Alain J
Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Ruymann Kathryn R
Department of Pediatrics, Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Farber Donna L
Department of Surgery and the Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA.
Sleiman Patrick M
Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Division of Human Genetics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Hakonarson Hakon
Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Division of Human Genetics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cianferoni Antonella
Department of Pediatrics, Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Wang Mei-Lun
Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Spergel Jonathan M
Department of Pediatrics, Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Comeau Michael R
Inflammation Research, Amgen Inc., Seattle, WA 98119, USA.
Artis David
Department of Microbiology, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: dartis@mail.med.upenn.edu.
References (52)
52 references, click to expand
  1. Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP.
    Nat Immunol. 2002 Jul;3(7):673-80 PMID: 12055625
  2. New paradigms in type 2 immunity.
    Science. 2012 Jul 27;337(6093):431-5 PMID: 22837519
  3. Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells.
    J Exp Med. 2007 Feb 19;204(2):253-8 PMID: 17242164
  4. Thymic stromal lymphopoietin (TSLP) is associated with allergic rhinitis in children with asthma.
    Clin Mol Allergy. 2011 Jan 18;9:1 PMID: 21244681
  5. Welcome to the neighborhood: epithelial cell-derived cytokines license innate and adaptive immune responses at mucosal sites.
    Immunol Rev. 2008 Dec;226:172-90 PMID: 19161424
  6. TSLP promotes interleukin-3-independent basophil haematopoiesis and type 2 inflammation.
    Nature. 2011 Aug 14;477(7363):229-33 PMID: 21841801
  7. Innate lymphoid cells wield a double-edged sword.
    Nat Immunol. 2011 Oct 19;12(11):1025-7 PMID: 22012433
  8. Pluripotent stem cell-based cancer therapy: promise and challenges.
    Sci Transl Med. 2012 Mar 28;4(127):127ps9 PMID: 22461639
  9. Hematopoietic progenitor cells are innate Th2 cytokine-producing cells.
    Allergy. 2012 Jan;67(1):4-9 PMID: 21884534
  10. Regulation of hematopoietic stem cell activity by inflammation.
    Front Immunol. 2013 Jul 19;4:204 PMID: 23882270
  11. Innate lymphoid cells--how did we miss them?
    Nat Rev Immunol. 2013 Feb;13(2):75-87 PMID: 23292121
  12. Critical role of P1-Runx1 in mouse basophil development.
    Blood. 2012 Jul 5;120(1):76-85 PMID: 22611151
  13. Dysregulated hematopoietic stem and progenitor cell activity promotes interleukin-23-driven chronic intestinal inflammation.
    Immunity. 2012 Dec 14;37(6):1116-29 PMID: 23200826
  14. The promise of induced pluripotent stem cells in research and therapy.
    Nature. 2012 Jan 18;481(7381):295-305 PMID: 22258608
  15. Thymic stromal lymphopoietin-elicited basophil responses promote eosinophilic esophagitis.
    Nat Med. 2013 Aug;19(8):1005-13 PMID: 23872715
  16. Comparison of in vitro drug-sensitivity of human granulocyte-macrophage progenitors from two different origins: umbilical cord blood and bone marrow.
    Exp Hematol. 1999 Nov;27(11):1593-8 PMID: 10560906
  17. IL25 elicits a multipotent progenitor cell population that promotes T(H)2 cytokine responses.
    Nature. 2010 Apr 29;464(7293):1362-6 PMID: 20200520
  18. Innate lymphoid cells--a proposal for uniform nomenclature.
    Nat Rev Immunol. 2013 Feb;13(2):145-9 PMID: 23348417
  19. Sensing the outside world: TSLP regulates barrier immunity.
    Nat Immunol. 2010 Apr;11(4):289-93 PMID: 20300138
  20. Thymic stromal lymphopoietin gene promoter polymorphisms are associated with susceptibility to bronchial asthma.
    Am J Respir Cell Mol Biol. 2011 Jun;44(6):787-93 PMID: 20656951
  21. Thymic stromal lymphopoietin-dependent basophils promote Th2 cytokine responses following intestinal helminth infection.
    J Immunol. 2012 Nov 1;189(9):4371-8 PMID: 23024277
  22. Human thymic stromal lymphopoietin preferentially stimulates myeloid cells.
    J Immunol. 2001 Jul 1;167(1):336-43 PMID: 11418668
  23. CD34+ hemopoietic progenitor cells are potent effectors of allergic inflammation.
    J Allergy Clin Immunol. 2009 Feb;123(2):472-8 PMID: 19064280
  24. Variants of thymic stromal lymphopoietin and its receptor associate with eosinophilic esophagitis.
    J Allergy Clin Immunol. 2010 Jul;126(1):160-5.e3 PMID: 20620568
  25. In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells.
    Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):3120-5 PMID: 10077647
  26. Innate immunity as orchestrator of stem cell mobilization.
    Leukemia. 2010 Oct;24(10):1667-75 PMID: 20703253
  27. Extramedullary hematopoiesis in breast after neoadjuvant chemotherapy for breast carcinoma.
    Ann Clin Lab Sci. 2006 Autumn;36(4):475-8 PMID: 17127738
  28. Immunosurveillance by hematopoietic progenitor cells trafficking through blood, lymph, and peripheral tissues.
    Cell. 2007 Nov 30;131(5):994-1008 PMID: 18045540
  29. Developmental checkpoints of the basophil/mast cell lineages in adult murine hematopoiesis.
    Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18105-10 PMID: 16330751
  30. DAVID: Database for Annotation, Visualization, and Integrated Discovery.
    Genome Biol. 2003;4(5):P3 PMID: 12734009
  31. TSLP regulates intestinal immunity and inflammation in mouse models of helminth infection and colitis.
    J Exp Med. 2009 Mar 16;206(3):655-67 PMID: 19273626
  32. The OP9-DL1 system: generation of T-lymphocytes from embryonic or hematopoietic stem cells in vitro.
    Cold Spring Harb Protoc. 2009 Feb;2009(2):pdb.prot5156 PMID: 20147086
  33. TSLP and IL-7 use two different mechanisms to regulate human CD4+ T cell homeostasis.
    J Exp Med. 2009 Sep 28;206(10):2111-9 PMID: 19770269
  34. A role for thymic stromal lymphopoietin in CD4(+) T cell development.
    J Exp Med. 2004 Jul 19;200(2):159-68 PMID: 15263024
  35. Common variants at 5q22 associate with pediatric eosinophilic esophagitis.
    Nat Genet. 2010 Apr;42(4):289-91 PMID: 20208534
  36. Physiological migration of hematopoietic stem and progenitor cells.
    Science. 2001 Nov 30;294(5548):1933-6 PMID: 11729320
  37. Toll-like receptors on hematopoietic progenitor cells stimulate innate immune system replenishment.
    Immunity. 2006 Jun;24(6):801-812 PMID: 16782035
  38. Innate lymphoid cells: emerging insights in development, lineage relationships, and function.
    Annu Rev Immunol. 2012;30:647-75 PMID: 22224763
  39. TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand.
    J Exp Med. 2005 Nov 7;202(9):1213-23 PMID: 16275760
  40. Extramedullary haematopoiesis in axillary lymph nodes following neoadjuvant chemotherapy for locally advanced breast cancer--a potential diagnostic pitfall.
    Histopathology. 2009 Apr;54(5):622-3 PMID: 19413641
  41. IL-25 simultaneously elicits distinct populations of innate lymphoid cells and multipotent progenitor type 2 (MPPtype2) cells.
    J Exp Med. 2013 Aug 26;210(9):1823-37 PMID: 23960191
  42. Hematopoietic stem cell and progenitor defects in Sca-1/Ly-6A-null mice.
    Blood. 2003 Jan 15;101(2):517-23 PMID: 12393491
  43. TSLP polymorphisms are associated with asthma in a sex-specific fashion.
    Allergy. 2010 Dec;65(12):1566-75 PMID: 20560908
  44. TSLP elicits IL-33-independent innate lymphoid cell responses to promote skin inflammation.
    Sci Transl Med. 2013 Jan 30;5(170):170ra16 PMID: 23363980
  45. Hematopoietic stem/progenitor cell mobilization. A continuing quest for etiologic mechanisms.
    Ann N Y Acad Sci. 1999 Apr 30;872:187-97; discussion 197-9 PMID: 10372122
  46. Quiescent haematopoietic stem cells are activated by IFN-gamma in response to chronic infection.
    Nature. 2010 Jun 10;465(7299):793-7 PMID: 20535209
  47. IL-33 induces IL-13 production by mouse mast cells independently of IgE-FcepsilonRI signals.
    J Leukoc Biol. 2007 Dec;82(6):1481-90 PMID: 17881510
  48. Demand-adapted regulation of early hematopoiesis in infection and inflammation.
    Blood. 2012 Mar 29;119(13):2991-3002 PMID: 22246037
  49. Identification of splenic reservoir monocytes and their deployment to inflammatory sites.
    Science. 2009 Jul 31;325(5940):612-6 PMID: 19644120
  50. Overexpression of murine TSLP impairs lymphopoiesis and myelopoiesis.
    Blood. 2004 Feb 1;103(3):843-51 PMID: 14512322
  51. Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation.
    J Exp Med. 2011 Mar 14;208(3):479-90 PMID: 21339324
  52. Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity.
    J Immunol. 2005 Jun 15;174(12):8183-90 PMID: 15944327
Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2013.09.016
Email
dartis@mail.med.upenn.edu
Published
2013-12-12
Pages
1158-70
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC3959827
Subset
IM
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NIAID NIH HHS · R01 AI095466 · United States
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Databases
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External Links
PubMed source DOI: 10.1016/j.immuni.2013.09.016 PMC Full Text View journal details
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