Total CD3 T Cells Are Necessary and Sufficient to Induce Colitis in Immunodeficient Mice With Dendritic Cell-Specific Deletion of TGFbR2: A Novel IBD Model to Study CD4 and CD8 T-Cell Interaction.
Inflamm Bowel Dis
; 26(2): 229-241, 2020 01 06.
Article
em En
| MEDLINE
| ID: mdl-31559420
ABSTRACT
BACKGROUND:
Inflammatory bowel disease (IBD) is a multifactorial disorder, with the innate and adaptive immune cells contributing to disease initiation and progression. However, the intricate cross-talk between immune cell lineages remains incompletely understood. The role of CD8+ T cells in IBD pathogenesis has been understudied, largely due to the lack of appropriate models.METHODS:
We previously reported spontaneous colitis in mice with impaired TGFß signaling due to dendritic cell-specific knockout of TGFbR2 (TGFßR2ΔDC). Here, we demonstrate that crossing TGFßR2ΔDC mice with a Rag1-/- background eliminates all symptoms of colitis and that adoptive transfer of unfractionated CD3+ splenocytes is sufficient to induce progressive colitis in Rag1-/-TGFßR2ΔDC mice.RESULTS:
Both CD4+ and CD8+ T cells are required for the induction of colitis accompanied by activation of both T-cell lineages and DCs, increased expression of mucosal IFNγ, TNFα, IL6, IL1ß, and IL12, and decreased frequencies of CD4+FoxP3+ regulatory T cells. Development of colitis required CD40L expression in CD4+ T cells, and the disease was partially ameliorated by IFNγ neutralization.CONCLUSIONS:
This novel model provides an important tool for studying IBD pathogenesis, in particular the complex interactions among innate and adaptive immune cells in a controlled fashion, and represents a valuable tool for preclinical evaluation of novel therapeutics.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
/
Linfócitos T CD4-Positivos
/
Complexo CD3
/
Colite
/
Linfócitos T CD8-Positivos
/
Modelos Animais de Doenças
/
Receptor do Fator de Crescimento Transformador beta Tipo II
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Inflamm Bowel Dis
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos