title: Role of the gut-associated and secondary lymphoid tissue in the induction of chronic colitis.
abstract: BACKGROUND
  It is well known that enteric bacterial antigens drive the development of chronic colitis in a variety of different mouse models of the inflammatory bowel diseases (IBD). The objective of this study was to evaluate the role of gut-associated lymphoid tissue (GALT; Peyer's patches, isolated lymphoid follicles), mesenteric lymph nodes (MLNs) and spleen in the pathogenesis of chronic colitis in mice.
  
  
  METHODS
  Surgical as well as genetic approaches were used to generate lymphopenic mice devoid of one or more of these lymphoid tissues. For the first series of studies, we subjected recombinase activating gene-1-deficient mice (RAG(-/-) ) to sham surgery (Sham), mesenteric lymphadenectomy (MLNx), splenectomy (Splx) or both (MLNx/Splx). In a second series of studies we intercrossed lymphotoxinβ-deficient (LTβ(-/-) ) mice with RAG(-/-) animals to generate LTβ(-/-) x RAG(-/-) offspring that were anticipated to contain functional MLNs but be devoid of GALT and most peripheral lymph nodes. Flow purified naïve (CD4(+) CD45RB(high) ) T-cells were adoptively transferred into the different groups of RAG(-/-) recipients to induce chronic colitis.
  
  
  RESULTS
  We found that at 3-5 wks following T-cell transfer, all four of the surgically-manipulated RAG(-/-) groups (Sham, MLNx, Splx and MLNx/Splx) developed chronic colitis that was similar in onset and severity. Flow cytometric analysis revealed no differences among the different groups with respect to surface expression of different gut-homing markers nor were there any differences noted in IFN-γ and IL-17 generation by mononuclear cells isolated among these surgically-manipulated mice. Although we anticipated that LTβ(-/-) x RAG(-/-) mice would contain functional MLNs but be devoid of GALT and peripheral lymph nodes (PLNs), we found that LTβ(-/-) x RAG(-/-) mice were in fact devoid of MLNs as well as GALT and PLNs. Adoptive transfer of CD45RB(high) T-cells into LTβ(-/-) x RAG(-/-) mice or their littermate controls (LTβ(+/+) x RAG(-/-) ) induced rapid and severe colitis in both groups.
  
  
  CONCLUSIONS
  Taken together, our data demonstrate that: a) neither the GALT, MLNs nor PLNs are required for induction of chronic gut inflammation in this model of IBD and b) T-and/or B-cells may be required for the development of MLNs in LTβ(-/-) mice.
authors.affiliation: Immunology and Inflammation Research Group LSU Health Sciences Center, Shreveport, Louisiana, USA.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takebayashi
authors.forename: Iurii
authors.initials: I
authors.lastname: Koboziev
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Ostanin
authors.forename: Laura
authors.initials: L
authors.lastname: Gray
authors.forename: Fridrik
authors.initials: F
authors.lastname: Karlsson
authors.forename: Sherry A
authors.initials: SA
authors.lastname: Robinson-Jackson
authors.forename: Melissa
authors.initials: M
authors.lastname: Kosloski-Davidson
authors.forename: Angela Burrows
authors.initials: AB
authors.lastname: Dooley
authors.forename: Songlin
authors.initials: S
authors.lastname: Zhang
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Grisham
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003092:Colitis / Q000209:etiology*; D005260:Female; D018398:Homeodomain Proteins / Q000502:physiology*; D020381:Interleukin-17 / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008221:Lymphoid Tissue; D053308:Lymphotoxin-beta / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010581:Peyer's Patches; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
chemical_list: D018398:Homeodomain Proteins; D020381:Interleukin-17; C505887:Ltb protein, mouse; D053308:Lymphotoxin-beta; C064658:RAG-1 protein
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