Journal Article
. 2018 Sep; 99(4):189-198.
doi: 10.1111/iep.12286.

A histomorphometric classification system for normal and inflamed mouse duodenum-Quali-quantitative approach

Airton Pereira E Silva 1 João R A Soares 1 Erika Bertozzi de Aquino Mattos 1 Claudia Josetti 1 Isabelle M Guimarães 1 Sylvia M N Campos 1 Gerlinde A P B Teixeira 1 
  • PMID: 30175413
  •     53 References
  •     1 citations


Gut-associated intestinal lymphoid tissue, the largest secondary lymphoid organ in the human body, constantly samples antigens from the gut lumen, presenting as a default response the activation of TCD4+ FOXP3+ regulatory T cells that secrete a profile of anti-inflammatory cytokines maintaining gut homeostasis denominated from an immunological perspective as mucosal tolerance. However, when antigens are sampled in an inflammatory setting, the immune response may either be protective, in the case of harmful pathogens, or cause further inflammatory reactions as in food allergy, inflammatory bowel diseases, coeliac disease or food protein-induced enterocolitis syndrome. Therefore, there is a need for accurate and consistent experimental models. However, a drawback in comparing these models is the lack of a classification system similar to that which is already used for humans. Thus, the aim of this work was to propose a classification system of the small intestinal histomorphology in experimental mice. To do this we used a mouse antigen-specific gut inflammation model developed by our research group. Duodenum sections stained with haematoxylin-eosin and Alcian blue were scanned using the APERIO scanning system and analysed with the ImageScope® software. The evaluated parameters were villus area, villus height and width, enterocyte count, mononuclear intra-epithelial leucocyte and goblet cell counts, and architectural and cellular ratios. Food-sensitized animals challenged with a diet containing the corresponding food allergen presented, as for humans, time-dependent shortened and widened villi accompanied by leucocyte infiltrate and loss of goblet cells. With these data, we were able to establish a classification system for experimental intestinal inflammation in mice thus permitting better comparisons among and between experiments than has been possible previously.

Keywords: food allergy; gut inflammation; inflammation score; mouse.

Differences in goblet cell differentiation between Crohn's disease and ulcerative colitis.
Michael Gersemann, Svetlana Becker, +9 authors, Eduard Friedrich Stange.
Differentiation, 2009 Mar 14; 77(1). PMID: 19281767
Three cheers for the goblet cell: maintaining homeostasis in mucosal epithelia.
Heather A McCauley, Géraldine Guasch.
Trends Mol Med, 2015 Jul 07; 21(8). PMID: 26144290
Celiac disease: From pathophysiology to treatment.
Ilaria Parzanese, Dorina Qehajaj, +5 authors, Fabio Grizzi.
World J Gastrointest Pathophysiol, 2017 Jun 03; 8(2). PMID: 28573065    Free PMC article.
Inflammatory bowel disease in adolescents.
Zubin Grover, Angela De Nardi, Peter J Lewindon.
Aust Fam Physician, 2017 Aug 09; 46(8). PMID: 28787555
Intestinal goblet cells and mucins in health and disease: recent insights and progress.
Young S Kim, Samuel B Ho.
Curr Gastroenterol Rep, 2010 Aug 13; 12(5). PMID: 20703838    Free PMC article.
Highly Cited. Review.
Comparison between digital and optical microscopy: Analysis in a mouse gut inflammation model.
Airton Pereira E Silva, Sylvia Maria Nicolau Campos, Isabelle Mazza Guimarães, Gerlinde Agate Platais Brasil Teixeira.
Biomed Rep, 2017 Sep 13; 7(3). PMID: 28894572    Free PMC article.
Role of Th17 Cells in the Pathogenesis of Human IBD.
Julio Gálvez.
ISRN Inflamm, 2014 Aug 08; 2014. PMID: 25101191    Free PMC article.
Highly Cited. Review.
Suppression of asthma-like responses in different mouse strains by oral tolerance.
M Russo, M A Nahori, +8 authors, B B Vargaftig.
Am J Respir Cell Mol Biol, 2001 May 15; 24(5). PMID: 11350820
Coeliac disease.
Benjamin Lebwohl, David S Sanders, Peter H R Green.
Lancet, 2017 Aug 02; 391(10115). PMID: 28760445
Highly Cited. Review.
A histomorphometric classification system for normal and inflamed mouse duodenum-Quali-quantitative approach.
Airton Pereira E Silva, João R A Soares, +4 authors, Gerlinde A P B Teixeira.
Int J Exp Pathol, 2018 Sep 04; 99(4). PMID: 30175413    Free PMC article.
An overview of randomization techniques: An unbiased assessment of outcome in clinical research.
Kp Suresh.
J Hum Reprod Sci, 2011 Jul 21; 4(1). PMID: 21772732    Free PMC article.
Highly Cited.
Oral administration of an edible-mushroom-derived protein inhibits the development of food-allergic reactions in mice.
K Y Hsieh, C I Hsu, +2 authors, R H Lin.
Clin Exp Allergy, 2003 Nov 18; 33(11). PMID: 14616874
Impairing oral tolerance promotes allergy and anaphylaxis: a new murine food allergy model.
Kirthana Ganeshan, Colleen V Neilsen, +3 authors, Paul J Bryce.
J Allergy Clin Immunol, 2008 Nov 22; 123(1). PMID: 19022495    Free PMC article.
Oral gene delivery with chitosan--DNA nanoparticles generates immunologic protection in a murine model of peanut allergy.
K Roy, H Q Mao, S K Huang, K W Leong.
Nat Med, 1999 Apr 15; 5(4). PMID: 10202926
Highly Cited.
Celiac disease: prevalence, diagnosis, pathogenesis and treatment.
Naiyana Gujral, Hugh J Freeman, Alan B R Thomson.
World J Gastroenterol, 2012 Nov 17; 18(42). PMID: 23155333    Free PMC article.
Highly Cited. Review.
Development and maintenance of intestinal regulatory T cells.
Takeshi Tanoue, Koji Atarashi, Kenya Honda.
Nat Rev Immunol, 2016 Apr 19; 16(5). PMID: 27087661
Highly Cited. Review.
Food allergy and the gut.
Anna Nowak-Wegrzyn, Hania Szajewska, Gideon Lack.
Nat Rev Gastroenterol Hepatol, 2016 Dec 22; 14(4). PMID: 27999436
Small intestine inflammation in Roquin-mutant and Roquin-deficient mice.
Jeremy S Schaefer, Dina Montufar-Solis, +2 authors, John R Klein.
PLoS One, 2013 Mar 02; 8(2). PMID: 23451046    Free PMC article.
Coeliac disease: the histology report.
Vincenzo Villanacci, Paola Ceppa, +4 authors, Società Italiana di Anatomia Patologica e Citopatologia Diagnostica/International Academy of Pathology, Italian division (SIAPEC/IAP).
Dig Liver Dis, 2011 Apr 07; 43 Suppl 4. PMID: 21459344
Small-intestinal histopathology and mortality risk in celiac disease.
Jonas F Ludvigsson, Scott M Montgomery, +2 authors, Fredrik Granath.
JAMA, 2009 Sep 17; 302(11). PMID: 19755695
Highly Cited.
Oral tolerance to food protein.
O Pabst, A M Mowat.
Mucosal Immunol, 2012 Feb 10; 5(3). PMID: 22318493    Free PMC article.
Highly Cited. Review.
Increasing Incidence and Altered Presentation in a Population-based Study of Pediatric Celiac Disease in North America.
Eyad Almallouhi, Katherine S King, +4 authors, Imad Absah.
J Pediatr Gastroenterol Nutr, 2017 Feb 06; 65(4). PMID: 28151767    Free PMC article.
Mechanisms of Tolerance Induction.
Anna Nowak-Węgrzyn, Pantipa Chatchatee.
Ann Nutr Metab, 2017 May 19; 70 Suppl 2. PMID: 28521317
Maternal immunomodulation of the offspring's immunological system.
Sylvia M N Campos, Vivian L de Oliveira, +4 authors, Gerlinde Agate Platais Brasil Teixeira.
Immunobiology, 2014 Aug 12; 219(11). PMID: 25104403
Current advances of murine models for food allergy.
Tiange Liu, Severine Navarro, Andreas L Lopata.
Mol Immunol, 2016 Jan 14; 70. PMID: 26759987
The histopathology of coeliac disease: time for a standardized report scheme for pathologists.
G Oberhuber, G Granditsch, H Vogelsang.
Eur J Gastroenterol Hepatol, 1999 Oct 19; 11(10). PMID: 10524652
Highly Cited. Review.
A novel model of sensitization and oral tolerance to peanut protein.
Jessica Strid, Melanie Thomson, +2 authors, Stephan Strobel.
Immunology, 2004 Oct 27; 113(3). PMID: 15500615    Free PMC article.
Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research.
Carol Kilkenny, William J Browne, +2 authors, Douglas G Altman.
PLoS Biol, 2010 Jul 09; 8(6). PMID: 20613859    Free PMC article.
Highly Cited. Review.
Child with Allergies or Allergic Reactions.
Reshma A, Arun K Baranwal.
Indian J Pediatr, 2017 Sep 12; 85(1). PMID: 28890990
Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota.
Koji Atarashi, Takeshi Tanoue, +19 authors, Kenya Honda.
Nature, 2013 Jul 12; 500(7461). PMID: 23842501
Highly Cited.
Engineered recombinant ovomucoid third domain can desensitize Balb/c mice of egg allergy.
P Rupa, Y Mine.
Allergy, 2006 Jun 24; 61(7). PMID: 16792581
Gastrointestinal considerations related to youth sports and the young athlete.
Garrett Koon, Orhan Atay, Sameer Lapsia.
Transl Pediatr, 2017 Aug 11; 6(3). PMID: 28795002    Free PMC article.
Diet selection in immunologically manipulated mice.
Gerlinde Teixeira, Patrícia Olaya Paschoal, +4 authors, Alberto Nóbrega.
Immunobiology, 2008 Jan 22; 213(1). PMID: 18207023
Contemporary celiac disease diagnosis: is a biopsy avoidable?
John R Mills, Joseph A Murray.
Curr Opin Gastroenterol, 2016 Jan 20; 32(2). PMID: 26784474
CD4+ T cells drive goblet cell depletion during Citrobacter rodentium infection.
Justin M Chan, Ganive Bhinder, +4 authors, Bruce A Vallance.
Infect Immun, 2013 Oct 09; 81(12). PMID: 24101690    Free PMC article.
Duodenal intraepithelial lymphocyte-count revisited.
B Veress, L Franzén, L Bodin, K Borch.
Scand J Gastroenterol, 2004 Mar 06; 39(2). PMID: 15000275
Oral mucosal immunity.
L Feller, M Altini, +3 authors, J Lemmer.
Oral Surg Oral Med Oral Pathol Oral Radiol, 2013 Oct 15; 116(5). PMID: 24119522
The measurement of villus cell population size in the mouse small intestine in normal and abnormal states: a comparison of absolute measurements with morphometric estimators in sectioned immersion-fixed material.
N A Wright, J Carter, M Irwin.
Cell Tissue Kinet, 1989 Nov 01; 22(6). PMID: 2611855
EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy.
A Muraro, T Werfel, +34 authors, EAACI Food Allergy and Anaphylaxis Guidelines Group.
Allergy, 2014 Jun 10; 69(8). PMID: 24909706
Highly Cited.
Histopathology of celiac disease.
G Oberhuber.
Biomed Pharmacother, 2000 Sep 16; 54(7). PMID: 10989975
Vaccination with recombinant modified vaccinia virus Ankara prevents the onset of intestinal allergy in mice.
C Bohnen, A Wangorsch, +11 authors, S Vieths.
Allergy, 2013 Aug 06; 68(8). PMID: 23909913
The food resource of adult Heligmosomoides polygyrus in the small intestine.
A D Bansemir, M V Sukhdeo.
J Parasitol, 1994 Feb 01; 80(1). PMID: 8308654
Celiac Disease and Other Causes of Duodenitis.
Daniel R Owen, David A Owen.
Arch Pathol Lab Med, 2017 Aug 02; 142(1). PMID: 28758791
Food allergy/hypersensitivity: antigenicity or timing?
Patrícia Olaya Paschoal, Sylvia M N Campos, +5 authors, Gerlinde Teixeira.
Immunobiology, 2009 Mar 31; 214(4). PMID: 19327544
Morphometric and immunohistochemical study of jejunal biopsies from children with intestinal soy allergy.
M Perkkiö, E Savilahti, P Kuitunen.
Eur J Pediatr, 1981 Sep 01; 137(1). PMID: 7196837
A guide to histomorphological evaluation of intestinal inflammation in mouse models.
Ulrike Erben, Christoph Loddenkemper, +6 authors, Anja A Kühl.
Int J Clin Exp Pathol, 2014 Sep 10; 7(8). PMID: 25197329    Free PMC article.
Highly Cited.
A murine model of IgE-mediated cow's milk hypersensitivity.
X M Li, B H Schofield, +2 authors, H A Sampson.
J Allergy Clin Immunol, 1999 Feb 09; 103(2 Pt 1). PMID: 9949309
Duodenal intraepithelial T lymphocytes in patients with functional dyspepsia.
Gilles Gargala, Stéphane Lecleire, +5 authors, Philippe Ducrotté.
World J Gastroenterol, 2007 May 19; 13(16). PMID: 17511033    Free PMC article.
[Diagnosis of celiac disease in adults].
Tatiana Sudbrack da Gama e Silva, Tania Weber Furlanetto.
Rev Assoc Med Bras (1992), 2010 Mar 27; 56(1). PMID: 20339798
Strain-specific helper T cell profile in the gut-associated lymphoid tissue.
Suzana Stanisavljević, Neda Đedović, +6 authors, Ivana Stojanović.
Immunol Lett, 2017 Aug 31; 190. PMID: 28851631
Oberhuber versus Marsh: much ado about nothing?
Amitabh Srivastava.
Gastroenterol Hepatol Bed Bench, 2015 Oct 16; 8(4). PMID: 26468343    Free PMC article.
Preventive and therapeutic effects of rapamycin, a mammalian target of rapamycin inhibitor, on food allergy in mice.
K Yamaki, S Yoshino.
Allergy, 2012 Aug 24; 67(10). PMID: 22913509
Modulation of intestinal goblet cell function during infection by an attaching and effacing bacterial pathogen.
Kirk S B Bergstrom, Julian A Guttman, +6 authors, Bruce A Vallance.
Infect Immun, 2007 Nov 07; 76(2). PMID: 17984203    Free PMC article.
A histomorphometric classification system for normal and inflamed mouse duodenum-Quali-quantitative approach.
Airton Pereira E Silva, João R A Soares, +4 authors, Gerlinde A P B Teixeira.
Int J Exp Pathol, 2018 Sep 04; 99(4). PMID: 30175413    Free PMC article.