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.
Fritsch Fredin
M
M
Department of Integrative Pharmacology, AstraZeneca R&D Mölndal, Mölndal, Sweden.
Elgbratt
K
K
Svensson
D
D
Jansson
L
L
Melgar
S
S
Hultgren Hörnquist
E
E
D000208:Acute Disease; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D016264:Dextran Sulfate / Q000008:administration & dosage*; D016130:Immunophenotyping; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D008231:Lymphopenia / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology / Q000473:pathology*
D016264:Dextran Sulfate