title: Epicutaneous sensitization results in IgE-dependent intestinal mast cell expansion and food-induced anaphylaxis.
abstract: BACKGROUND
  Sensitization to food antigen can occur through cutaneous exposure.
  
  
  OBJECTIVE
  We sought to test the hypothesis that epicutaneous sensitization with food antigen predisposes to IgE-mediated anaphylaxis on oral allergen challenge.
  
  
  METHODS
  BALB/c mice were epicutaneously sensitized by repeated application of ovalbumin (OVA) to tape-stripped skin over 7 weeks or orally immunized with OVA and cholera toxin (CT) weekly for 8 weeks and then orally challenged with OVA. Body temperature was monitored, and serum mouse mast cell protease 1 levels were determined after challenge. Tissue mast cell (MC) counts were examined by using chloroacetate esterase staining. Levels of serum OVA-specific IgE and IgG(1) antibodies and cytokines in supernatants of OVA-stimulated splenocytes were measured by means of ELISA. Serum IL-4 levels were measured by using an in vivo cytokine capture assay.
  
  
  RESULTS
  Epicutaneously sensitized mice exhibited expansion of connective tissue MCs in the jejunum, increased serum IL-4 levels, and systemic anaphylaxis after oral challenge, as evidenced by decreased body temperature and increased serum mouse mast cell protease 1 levels. Intestinal MC expansion and anaphylaxis were IgE dependent because they did not occur in epicutaneously sensitized IgE(-/-) mice. Mice orally immunized with OVA plus CT did not have increased serum IL-4 levels, expanded intestinal MCs, or anaphylaxis after oral challenge, despite OVA-specific IgE levels and splenocyte cytokine production in response to OVA stimulation, which were comparable with those of epicutaneously sensitized mice.
  
  
  CONCLUSIONS
  Epicutaneously sensitized mice, but not mice orally immunized with antigen plus CT, have expansion of intestinal MCs and IgE-mediated anaphylaxis after single oral antigen challenge. IgE is necessary but not sufficient for food anaphylaxis, and MC expansion in the gut can play an important role in the development of anaphylaxis.
authors: Division of Immunology, Boston Children's Hospital, Boston, Mass 02115, USA.
authors: Lisa M
authors: LM
authors: Bartnikas
authors: Michael F
authors: MF
authors: Gurish
authors: Oliver T
authors: OT
authors: Burton
authors: Sabine
authors: S
authors: Leisten
authors: Erin
authors: E
authors: Janssen
authors: Hans C
authors: HC
authors: Oettgen
authors: Jacqueline
authors: J
authors: Beaupré
authors: Christopher N
authors: CN
authors: Lewis
authors: K Frank
authors: KF
authors: Austen
authors: Stephanie
authors: S
authors: Schulte
authors: Jason L
authors: JL
authors: Hornick
authors: Raif S
authors: RS
authors: Geha
authors: Michiko K
authors: MK
authors: Oyoshi
mesh_terms: D000279:Administration, Cutaneous; D000485:Allergens / Q000276:immunology; D000707:Anaphylaxis / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001831:Body Temperature / Q000276:immunology; D018932:Chemokine CCL2 / Q000276:immunology; D002772:Cholera Toxin / Q000276:immunology; D005512:Food Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D007583:Jejunum / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D012867:Skin / Q000276:immunology*
chemical_list: D000485:Allergens; D000906:Antibodies; D000941:Antigens; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D007074:Immunoglobulin G; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin; D002772:Cholera Toxin
references: Int Arch Allergy Immunol. 2004 Oct;135(2):108-16
references: 15345909
references: J Immunol. 2007 Apr 1;178(7):4177-83
references: 17371974
references: J Immunol. 2005 Jun 1;174(11):6751-6
references: 15905515
references: J Allergy Clin Immunol. 2010 Nov;126(5):976-84, 984.e1-5
references: 21050944
references: Immunol Rev. 2001 Feb;179:82-93
references: 11292031
references: J Clin Invest. 1998 Apr 15;101(8):1614-22
references: 9541491
references: J Immunol. 2009 Feb 15;182(4):2416-24
references: 19201896
references: J Allergy Clin Immunol. 2009 Jul;124(1):3-20; quiz 21-2
references: 19560575
references: Mol Immunol. 2008 May;45(9):2548-58
references: 18313755
references: J Pediatr. 2007 Oct;151(4):359-63
references: 17889069
references: J Immunol. 2011 May 15;186(10):5629-37
references: 21490160
references: N Engl J Med. 2003 Mar 13;348(11):977-85
references: 12637607
references: Allergy. 2011 Aug;66(8):1038-46
references: 21426359
references: J Immunol. 2003 Apr 1;170(7):3835-42
references: 12646651
references: J Allergy Clin Immunol. 2009 Jan;123(1):231-238.e4
references: 19022495
references: J Allergy Clin Immunol. 2009 Apr;123(4):875-82.e1
references: 19348925
references: Immunology. 2011 Dec;134(4):378-85
references: 22044021
references: Nature. 2010 Apr 29;464(7293):1367-70
references: 20200518
references: Immunology. 1999 Jan;96(1):138-44
references: 10233688
references: Curr Protoc Immunol. 2003 Aug;Chapter 6:Unit 6.28
references: 18432911
references: J Allergy Clin Immunol. 2010 Feb;125(2):469-476.e2
references: 20159257
references: J Allergy Clin Immunol. 2011 Mar;127(3):795-805.e1-6
references: 21167580
references: J Allergy Clin Immunol. 2010 Dec;126(6 Suppl):S1-58
references: 21134576
references: Pediatrics. 1998 Mar;101(3):E8
references: 9481027
references: J Clin Invest. 2011 Aug;121(8):3051-61
references: 21737878
references: J Clin Invest. 2003 Dec;112(11):1666-77
references: 14660743
references: Immunol Rev. 2005 Aug;206:204-18
references: 16048551
references: J Cell Biol. 1996 Oct;135(1):279-90
references: 8858180
references: Scand J Immunol. 2006 Sep;64(3):251-9
references: 16918694
references: Gastroenterology. 2006 Jul;131(1):47-58
references: 16831589
references: J Clin Invest. 2011 Jun;121(6):2210-20
references: 21537081
references: J Immunol. 2006 Dec 1;177(11):7634-44
references: 17114433
references: J Allergy Clin Immunol. 2008 Nov;122(5):984-91
references: 19000582
references: J Exp Med. 2008 Apr 14;205(4):897-913
references: 18378796
references: Immunol Lett. 2008 Nov 16;121(1):45-51
references: 18824031
references: Clin Exp Allergy. 2010 Jul;40(7):965-72
references: 20642575
references: Science. 2011 Jan 21;331(6015):337-41
references: 21205640
references: Proc Natl Acad Sci U S A. 2011 Aug 23;108(34):14210-5
references: 21825171
references: Clin Exp Allergy. 2010 Jan;40(1):153-62
references: 19689461
references: J Invest Dermatol. 2009 Jan;129(1):31-40
references: 19078986
references: Nature. 1994 Aug 4;370(6488):367-70
references: 8047141
references: Clin Exp Allergy. 2011 Jan;41(1):20-8
references: 21070397
references: J Allergy Clin Immunol. 2011 Mar;127(3):661-7
references: 21377035
references: J Allergy Clin Immunol. 2007 Sep;120(3):506-15; quiz 516-7
references: 17765751
references: Allergy. 2006 Jan;61(1):64-71
references: 16364158
references: Exp Dermatol. 1997 Apr;6(2):98-104
references: 9209892
references: Scand J Immunol. 2007 Aug-Sep;66(2-3):278-86
references: 17635805
references: Immunity. 2008 Nov 14;29(5):771-81
references: 18993084
references: Clin Exp Allergy. 2003 Aug;33(8):1067-75
references: 12911780
references: J Immunol. 2004 Jun 1;172(11):6978-87
references: 15153518