Immunologic Research

, Volume 47, Issue 1–3, pp 3–13 | Cite as

Tyrosine phosphatase SHP-1 in allergic and anaphylactic inflammation

  • Zhou Zhu
  • Sun Young Oh
  • You Sook Cho
  • Li Zhang
  • Yoon-Keun Kim
  • Tao Zheng
Article

Abstract

Protein tyrosine phosphatase SHP-1 is an essential regulatory molecule in many different signaling pathways. The biological importance of SHP-1 is underscored by the motheaten mutant mouse strains with immunological disorders involving multiple organs and by the close association of aberrant SHP-1 expression with several human diseases. Recent studies provided some compelling evidence that supports a role of SHP-1 in regulating mast cell development and function and also in regulating type 2 allergic inflammatory responses in both innate and adaptive immune responses. In this article, we summarize the recent advancement of our understanding of this interesting phosphatase in the important area of allergic inflammation.

Keywords

Phosphatase Mast cells Th2 cytokines Allergic inflammatory response Allergy Asthma 

Abbreviations

BMMC

Bone marrow-derived mast cells

FcεRI

High-affinity Fc receptor for IgE

SCF

Stem cell factor or c-Kit ligand

me

Motheaten

mev

Viable motheaten

LAT2

Linker for activation of T cells 2, also called NTAL or LAB

References

  1. 1.
    Gilfillan AM, Rivera J. The tyrosine kinase network regulating mast cell activation. Immunol Rev. 2009;228:149–69.CrossRefPubMedGoogle Scholar
  2. 2.
    Lorenz U. SHP-1 and SHP-2 in T cells: two phosphatases functioning at many levels. Immunol Rev. 2009;228:342–59.CrossRefPubMedGoogle Scholar
  3. 3.
    Green MC, Shultz LD. Motheaten, an immunodeficient mutant of the mouse. I. Genetics and pathology. J Hered. 1975;66:250–8.PubMedGoogle Scholar
  4. 4.
    Shultz LD, et al. Mutations at the murine motheaten locus are within the hematopoietic cell protein-tyrosine phosphatase (Hcph) gene. Cell. 1993;73:1445–54.CrossRefPubMedGoogle Scholar
  5. 5.
    Tsui HW, Siminovitch KA, de Souza L, Tsui FW. Motheaten and viable motheaten mice have mutations in the haematopoietic cell phosphatase gene. Nat Genet. 1993;4:124–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Ward JM. Pulmonary pathology of the motheaten mouse. Vet Pathol. 1978;15:170–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Shultz LD, Coman DR, Bailey CL, Beamer WG, Sidman CL. “Viable motheaten”, a new allele at the motheaten locus. I. Pathology. Am J Pathol. 1984;116:179–92.PubMedGoogle Scholar
  8. 8.
    Rossi GA, Hunninghake GW, Kawanami O, Ferrans VJ, Hansen CT, Crystal RG. Motheaten mice–an animal model with an inherited form of interstitial lung disease. Am Rev Respir Dis. 1985;131:150–8.PubMedGoogle Scholar
  9. 9.
    Kovarik J, Kuntz L, Ryffel B, Borel JF. The viable motheaten (mev) mouse–a new model for arthritis. J Autoimmun. 1994;7:575–88.CrossRefPubMedGoogle Scholar
  10. 10.
    Oh SY, et al. A critical role of SHP-1 in regulation of type 2 inflammation in the lung. Am J Respir Cell Mol Biol. 2009;40:568–74.CrossRefPubMedGoogle Scholar
  11. 11.
    Kamata T, et al. src homology 2 domain-containing tyrosine phosphatase SHP-1 controls the development of allergic airway inflammation. J Clin Invest. 2003;111:109–19.PubMedGoogle Scholar
  12. 12.
    Cho YS, Oh SY, Zhu Z. Tyrosine phosphatase SHP-1 in oxidative stress and development of allergic airway inflammation. Am J Respir Cell Mol Biol. 2008;39:412–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Cunnick JM, Dorsey JF, Mei L, Wu J. Reversible regulation of SHP-1 tyrosine phosphatase activity by oxidation. Biochem Mol Biol Int. 1998;45:887–94.PubMedGoogle Scholar
  14. 14.
    Meng TC, Fukada T, Tonks NK. Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo. Mol Cell. 2002;9:387–99.CrossRefPubMedGoogle Scholar
  15. 15.
    Heneberg P, Draber P. Regulation of cys-based protein tyrosine phosphatases via reactive oxygen and nitrogen species in mast cells and basophils. Curr Med Chem. 2005;12:1859–71.CrossRefPubMedGoogle Scholar
  16. 16.
    Frossi B, De Carli M, Daniel KC, Rivera J, Pucillo C. Oxidative stress stimulates IL-4 and IL-6 production in mast cells by an APE/Ref-1-dependent pathway. Eur J Immunol. 2003;33:2168–77.CrossRefPubMedGoogle Scholar
  17. 17.
    Frossi B, Rivera J, Hirsch E, Pucillo C. Selective activation of Fyn/PI3K and p38 MAPK regulates IL-4 production in BMMC under nontoxic stress condition. J Immunol. 2007;178:2549–55.PubMedGoogle Scholar
  18. 18.
    Yu CC, Tsui HW, Ngan BY, Shulman MJ, Wu GE, Tsui FW. B and T cells are not required for the viable motheaten phenotype. J Exp Med. 1996;183:371–80.CrossRefPubMedGoogle Scholar
  19. 19.
    Paulson RF, Vesely S, Siminovitch KA, Bernstein A. Signalling by the W/Kit receptor tyrosine kinase is negatively regulated in vivo by the protein tyrosine phosphatase Shp1. Nat Genet. 1996;13:309–15.CrossRefPubMedGoogle Scholar
  20. 20.
    Lorenz U, et al. Genetic analysis reveals cell type-specific regulation of receptor tyrosine kinase c-Kit by the protein tyrosine phosphatase SHP1. J Exp Med. 1996;184:1111–26.CrossRefPubMedGoogle Scholar
  21. 21.
    Masuda A, Yoshikai Y, Aiba K, Matsuguchi T. Th2 cytokine production from mast cells is directly induced by lipopolysaccharide and distinctly regulated by c-Jun N-terminal kinase and p38 pathways. J Immunol. 2002;169:3801–10.PubMedGoogle Scholar
  22. 22.
    Pawankar R, Okuda M, Yssel H, Okumura K, Ra C. Nasal mast cells in perennial allergic rhinitics exhibit increased expression of the Fc epsilonRI, CD40L, IL-4, and IL-13, and can induce IgE synthesis in B cells. J Clin Invest. 1997;99:1492–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Brightling CE, Bradding P, Symon FA, Holgate ST, Wardlaw AJ, Pavord ID. Mast-cell infiltration of airway smooth muscle in asthma. N Engl J Med. 2002;346:1699–705.CrossRefPubMedGoogle Scholar
  24. 24.
    MacGlashan D Jr, White JM, Huang SK, Ono SJ, Schroeder JT, Lichtenstein LM. Secretion of IL-4 from human basophils. The relationship between IL-4 mRNA and protein in resting and stimulated basophils. J Immunol. 1994;152:3006–16.PubMedGoogle Scholar
  25. 25.
    Gibbs BF, et al. Purified human peripheral blood basophils release interleukin-13 and preformed interleukin-4 following immunological activation. Eur J Immunol. 1996;26:2493–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Redrup AC, Howard BP, MacGlashan DW Jr, Kagey-Sobotka A, Lichtenstein LM, Schroeder JT. Differential regulation of IL-4 and IL-13 secretion by human basophils: their relationship to histamine release in mixed leukocyte cultures. J Immunol. 1998;160:1957–64.PubMedGoogle Scholar
  27. 27.
    Rumbley CA, Sugaya H, Zekavat SA, El Refaei M, Perrin PJ, Phillips SM. Activated eosinophils are the major source of Th2-associated cytokines in the schistosome granuloma. J Immunol. 1999;162:1003–9.PubMedGoogle Scholar
  28. 28.
    Kimura T, Zhang J, Sagawa K, Sakaguchi K, Appella E, Siraganian RP. Syk-independent tyrosine phosphorylation and association of the protein tyrosine phosphatases SHP-1 and SHP-2 with the high affinity IgE receptor. J Immunol. 1997;159:4426–34.PubMedGoogle Scholar
  29. 29.
    Ozawa T, Nakata K, Mizuno K, Yakura H. Negative autoregulation of Src homology region 2-domain-containing phosphatase-1 in rat basophilic leukemia-2H3 cells. Int Immunol. 2007;19:1049–61.CrossRefPubMedGoogle Scholar
  30. 30.
    Nakata K, et al. Positive and negative regulation of high affinity IgE receptor signaling by Src homology region 2 domain-containing phosphatase 1. J Immunol. 2008;181:5414–24.PubMedGoogle Scholar
  31. 31.
    Xie ZH, Zhang J, Siraganian RP. Positive regulation of c-Jun N-terminal kinase and TNF-alpha production but not histamine release by SHP-1 in RBL-2H3 mast cells. J Immunol. 2000;164:1521–8.PubMedGoogle Scholar
  32. 32.
    Thrall RS, Vogel SN, Evans R, Shultz LD. Role of tumor necrosis factor-alpha in the spontaneous development of pulmonary fibrosis in viable motheaten mutant mice. Am J Pathol. 1997;151:1303–10.PubMedGoogle Scholar
  33. 33.
    Su X, Zhou T, Yang P, Edwards CK III, Mountz JD. Reduction of arthritis and pneumonitis in motheaten mice by soluble tumor necrosis factor receptor. Arthritis Rheum. 1998;41:139–49.CrossRefPubMedGoogle Scholar
  34. 34.
    Borner C. Diminished cell proliferation associated with the death-protective activity of Bcl-2. J Biol Chem. 1996;271:12695–8.PubMedGoogle Scholar
  35. 35.
    Hsu C, MacGlashan D Jr. IgE antibody up-regulates high affinity IgE binding on murine bone marrow-derived mast cells. Immunol Lett. 1996;52:129–34.CrossRefPubMedGoogle Scholar
  36. 36.
    Zhang L, Oh SY, Wu X, Oh MH, Wu F, Schroeder JT, et al. SHP-1 deficient mast cells are hyperresponsive to stimulation and critical in initiating allergic inflammation in the lung. J Immunol. 2009; ePub 2010/01/01.Google Scholar
  37. 37.
    Mertsching E, et al. A mouse Fcgamma-Fcepsilon protein that inhibits mast cells through activation of FcgammaRIIB, SH2 domain-containing inositol phosphatase 1, and SH2 domain-containing protein tyrosine phosphatases. J Allergy Clin Immunol. 2008;121:441–7.CrossRefPubMedGoogle Scholar
  38. 38.
    Fong DC, Malbec O, Arock M, Cambier JC, Fridman WH, Daeron M. Selective in vivo recruitment of the phosphatidylinositol phosphatase SHIP by phosphorylated Fc gammaRIIB during negative regulation of IgE-dependent mouse mast cell activation. Immunol Lett. 1996;54:83–91.CrossRefPubMedGoogle Scholar
  39. 39.
    Lu-Kuo JM, Joyal DM, Austen KF, Katz HR. gp49B1 inhibits IgE-initiated mast cell activation through both immunoreceptor tyrosine-based inhibitory motifs, recruitment of src homology 2 domain-containing phosphatase-1, and suppression of early and late calcium mobilization. J Biol Chem. 1999;274:5791–6.CrossRefPubMedGoogle Scholar
  40. 40.
    Daheshia M, Friend DS, Grusby MJ, Austen KF, Katz HR. Increased severity of local and systemic anaphylactic reactions in gp49B1-deficient mice. J Exp Med. 2001;194:227–34.CrossRefPubMedGoogle Scholar
  41. 41.
    Zhang Q, Raghunath PN, Vonderheid E, Odum N, Wasik MA. Lack of phosphotyrosine phosphatase SHP-1 expression in malignant T-cell lymphoma cells results from methylation of the SHP-1 promoter. Am J Pathol. 2000;157:1137–46.PubMedGoogle Scholar
  42. 42.
    Oka T, et al. Reduction of hematopoietic cell-specific tyrosine phosphatase SHP-1 gene expression in natural killer cell lymphoma and various types of lymphomas/leukemias : combination analysis with cDNA expression array and tissue microarray. Am J Pathol. 2001;159:1495–505.PubMedGoogle Scholar
  43. 43.
    Chim CS, Wong KY, Loong F, Srivastava G. SOCS1 and SHP1 hypermethylation in mantle cell lymphoma and follicular lymphoma: implications for epigenetic activation of the Jak/STAT pathway. Leukemia. 2004;18:356–8.CrossRefPubMedGoogle Scholar
  44. 44.
    Khoury JD, Rassidakis GZ, Medeiros LJ, Amin HM, Lai R. Methylation of SHP1 gene and loss of SHP1 protein expression are frequent in systemic anaplastic large cell lymphoma. Blood. 2004;104:1580–1.CrossRefPubMedGoogle Scholar
  45. 45.
    Zhang Q, Wang HY, Marzec M, Raghunath PN, Nagasawa T, Wasik MA. STAT3- and DNA methyltransferase 1-mediated epigenetic silencing of SHP-1 tyrosine phosphatase tumor suppressor gene in malignant T lymphocytes. Proc Natl Acad Sci U S A. 2005;102:6948–53.CrossRefPubMedGoogle Scholar
  46. 46.
    Reddy J, et al. Differential methylation of genes that regulate cytokine signaling in lymphoid and hematopoietic tumors. Oncogene. 2005;24:732–6.CrossRefPubMedGoogle Scholar
  47. 47.
    Wickrema A, et al. Defective expression of the SHP-1 phosphatase in polycythemia vera. Exp Hematol. 1999;27:1124–32.CrossRefPubMedGoogle Scholar
  48. 48.
    Asimakopoulos FA, et al. The gene encoding hematopoietic cell phosphatase (SHP-1) is structurally and transcriptionally intact in polycythemia vera. Oncogene. 1997;14:1215–22.CrossRefPubMedGoogle Scholar
  49. 49.
    Andersson P, LeBlanc K, Eriksson BA, Samuelsson J. No evidence for an altered mRNA expression or protein level of haematopoietic cell phosphatase in CD34+ bone marrow progenitor cells or mature peripheral blood cells in polycythaemia vera. Eur J Haematol. 1997;59:310–7.PubMedCrossRefGoogle Scholar
  50. 50.
    Amin HM, Hoshino K, Yang H, Lin Q, Lai R, Garcia-Manero G. Decreased expression level of SH2 domain-containing protein tyrosine phosphatase-1 (Shp1) is associated with progression of chronic myeloid leukaemia. J Pathol. 2007;212:402–10.CrossRefPubMedGoogle Scholar
  51. 51.
    Ruchusatsawat K, Wongpiyabovorn J, Shuangshoti S, Hirankarn N, Mutirangura A. SHP-1 promoter 2 methylation in normal epithelial tissues and demethylation in psoriasis. J Mol Med. 2006;84:175–82.CrossRefPubMedGoogle Scholar
  52. 52.
    Christophi GP, et al. SHP-1 deficiency and increased inflammatory gene expression in PBMCs of multiple sclerosis patients. Lab Invest. 2008;88:243–55.CrossRefPubMedGoogle Scholar
  53. 53.
    Christophi GP, et al. Macrophages of multiple sclerosis patients display deficient SHP-1 expression and enhanced inflammatory phenotype. Lab Invest. 2009;89:742–59.CrossRefPubMedGoogle Scholar
  54. 54.
    Deng C, et al. Expression of the tyrosine phosphatase SRC homology 2 domain-containing protein tyrosine phosphatase 1 determines T cell activation threshold and severity of experimental autoimmune encephalomyelitis. J Immunol. 2002;168:4511–8.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Zhou Zhu
    • 1
  • Sun Young Oh
    • 1
  • You Sook Cho
    • 1
  • Li Zhang
    • 1
  • Yoon-Keun Kim
    • 1
  • Tao Zheng
    • 1
  1. 1.Division of Allergy and Clinical Immunology, Johns Hopkins Asthma and Allergy CenterJohns Hopkins UniversityBaltimoreUSA

Personalised recommendations