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Role of the gut-associated and secondary lymphoid tissue in the induction of chronic colitis

Authors

  • Koichi Takebayashi MD,

    1. Immunology and Inflammation Research Group LSU Health Sciences Center, Shreveport, Louisiana
    2. Department of Molecular and Cellular Physiology LSU Health Sciences Center, Shreveport, Louisiana
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    • The first two authors contributed equally to this work.

  • Iurii Koboziev BS,

    1. Immunology and Inflammation Research Group LSU Health Sciences Center, Shreveport, Louisiana
    2. Department of Molecular and Cellular Physiology LSU Health Sciences Center, Shreveport, Louisiana
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    • The first two authors contributed equally to this work.

  • Dmitry V. Ostanin PhD,

    1. Immunology and Inflammation Research Group LSU Health Sciences Center, Shreveport, Louisiana
    2. Department of Medicine, Division of RheumatologyLSU Health Sciences Center, Shreveport, Louisiana
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  • Laura Gray BS,

    1. Immunology and Inflammation Research Group LSU Health Sciences Center, Shreveport, Louisiana
    2. Department of Molecular and Cellular Physiology LSU Health Sciences Center, Shreveport, Louisiana
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  • Fridrik Karlsson BS,

    1. Immunology and Inflammation Research Group LSU Health Sciences Center, Shreveport, Louisiana
    2. Department of Molecular and Cellular Physiology LSU Health Sciences Center, Shreveport, Louisiana
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  • Sherry A. Robinson-Jackson BS,

    1. Immunology and Inflammation Research Group LSU Health Sciences Center, Shreveport, Louisiana
    2. Department of Molecular and Cellular Physiology LSU Health Sciences Center, Shreveport, Louisiana
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  • Melissa Kosloski-Davidson BS,

    1. Immunology and Inflammation Research Group LSU Health Sciences Center, Shreveport, Louisiana
    2. Department of Molecular and Cellular Physiology LSU Health Sciences Center, Shreveport, Louisiana
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  • Angela Burrows Dooley BS,

    1. Immunology and Inflammation Research Group LSU Health Sciences Center, Shreveport, Louisiana
    2. Department of Molecular and Cellular Physiology LSU Health Sciences Center, Shreveport, Louisiana
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  • Songlin Zhang MD,

    1. Immunology and Inflammation Research Group LSU Health Sciences Center, Shreveport, Louisiana
    2. Department of Pathology, LSU Health Sciences Center, Shreveport, Louisiana
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  • Matthew B. Grisham PhD

    Corresponding author
    1. Immunology and Inflammation Research Group LSU Health Sciences Center, Shreveport, Louisiana
    2. Department of Molecular and Cellular Physiology LSU Health Sciences Center, Shreveport, Louisiana
    • Immunology and Inflammation Research Group, Department of Molecular and Cellular Physiology, LSU Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130
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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+CD45RBhigh) 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 CD45RBhigh 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. (Inflamm Bowel Dis 2011;)

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