Dextran sulfate sodium-induced colitis generates a transient thymic involution--impact on thymocyte subsets.

• One of the most widely used animal models for inflammatory bowel disease (IBD) is the dextran sulfate sodium (DSS)-induced colitis. We have previously reported that 5 days administration of DSS in C57Bl/6J mice induces a colonic inflammation that progresses into chronicity after DSS removal, whereas in BALB/cJ mice the inflammation resolves within 4 weeks post-DSS. Here we show that both thymic size and thymocyte numbers dramatically decreased in the acute phase of inflammation in C57Bl/6 mice, 7 days after DSS withdrawal. Mature, CD4(+) and CD8(+) single positive (SP) CD69(lo) CD62L(hi) thymocytes were enriched in these mice, accompanied by a major decrease in the number of immature double positive (DP) thymocytes. However, the different maturation stages within the DP thymocyte subset were unchanged between healthy and inflamed C57Bl/6J mice. Interestingly, as the inflammation progressed into the chronic phase, the thymus recovered and 2 weeks after the acute inflammatory phase all the thymic parameters investigated in this study were restored to normal. In contrast, BALB/cJ mice only develop mild thymic alterations. Nevertheless, we found that within the double negative (DN) thymocytes an increased frequency and also total numbers of CD44(+) CD25(-) (DN1) cells correlated with the severity of colitis, and that the frequency of CD44(-) CD25(-) (DN4) thymocytes decreased proportionally in the acute phase in BALB/cJ mice. Our observations suggest that the thymic effects are intimately connected to the intestinal inflammatory response in colitis regardless of the inflammatory stimuli.

Nyckelord

Acute Disease

Animals

Cell Differentiation

immunology

Chronic Disease

Colitis

chemically induced

immunology

pathology

Dextran Sulfate

administration & dosage

Immunophenotyping

Lymphocyte Subsets

drug effects

immunology

pathology

Lymphopenia

immunology

pathology

Mice

Mice

Inbred BALB C

Mice

Inbred C57BL

Severity of Illness Index

T-Lymphocyte Subsets

drug effects

immunology

pathology

Thymus Gland

drug effects

immunology

pathology

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