TY - JOUR
T1 - Roles of T cell-associated L-selectin and β7 integrins during induction and regulation of chronic colitis
AU - Kurmaeva, Elvira
AU - Boktor, Moheb
AU - Zhang, Songling
AU - Bao, Richard
AU - Berney, Seth
AU - Ostanin, Dmitry V.
PY - 2013/11/1
Y1 - 2013/11/1
N2 - Background: L-selectin (CD62L) and β7 integrins are important for trafficking of naive T cells under steady-state conditions. The objectives of this study were to dissect the requirements for T cell-associated CD62L and β7 integrins during initiation, progression, and regulation of chronic colitis. Methods: Using the T-cell transfer model, we compared colitogenic potential between T cells lacking one or both of these molecules with wild-type T cells. To assess trafficking of cells to the secondary lymphoid tissue and the gut, we performed co-homing experiments. Results: Adoptive transfer of wild-type, CD62L-/- or β7-/- single-deficient T cells induced moderate to severe disease with slightly different kinetics. However, transfer of CD62L -/- β7-/- double-deficient (DKO) T cells produced significantly attenuated gut inflammation, which correlated with fewer T cells and reduced levels of proinflammatory cytokines in the colon lamina propria. Our subsequent experiments established that lack of colitogenic potential of these cells was due to inability of DKO T cells to home to the secondary lymphoid tissue. Furthermore, homing of in vitro-generated effector DKO T cells to the inflamed intestine was significantly impaired. Lastly, DKO regulatory T cells were ineffective at suppressing colitis induced by wildtype T cells. Conclusions: We established that T cells can use either CD62L or β7 integrins to induce chronic colitis, but lack of both abrogates their colitogenic potential. Effector T cells critically rely on β7 integrin during their recruitment to the inflamed intestinal mucosa. Finally, regulation of intestinal inflammation by regulatory T cells requires one or both of these adhesion molecules.
AB - Background: L-selectin (CD62L) and β7 integrins are important for trafficking of naive T cells under steady-state conditions. The objectives of this study were to dissect the requirements for T cell-associated CD62L and β7 integrins during initiation, progression, and regulation of chronic colitis. Methods: Using the T-cell transfer model, we compared colitogenic potential between T cells lacking one or both of these molecules with wild-type T cells. To assess trafficking of cells to the secondary lymphoid tissue and the gut, we performed co-homing experiments. Results: Adoptive transfer of wild-type, CD62L-/- or β7-/- single-deficient T cells induced moderate to severe disease with slightly different kinetics. However, transfer of CD62L -/- β7-/- double-deficient (DKO) T cells produced significantly attenuated gut inflammation, which correlated with fewer T cells and reduced levels of proinflammatory cytokines in the colon lamina propria. Our subsequent experiments established that lack of colitogenic potential of these cells was due to inability of DKO T cells to home to the secondary lymphoid tissue. Furthermore, homing of in vitro-generated effector DKO T cells to the inflamed intestine was significantly impaired. Lastly, DKO regulatory T cells were ineffective at suppressing colitis induced by wildtype T cells. Conclusions: We established that T cells can use either CD62L or β7 integrins to induce chronic colitis, but lack of both abrogates their colitogenic potential. Effector T cells critically rely on β7 integrin during their recruitment to the inflamed intestinal mucosa. Finally, regulation of intestinal inflammation by regulatory T cells requires one or both of these adhesion molecules.
KW - Adhesion molecules
KW - Effector T cell
KW - Inflammation
KW - Inflammatory bowel disease
KW - Leukocyte trafficking
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U2 - 10.1097/MIB.0b013e3182a8df0a
DO - 10.1097/MIB.0b013e3182a8df0a
M3 - Article
C2 - 24132160
AN - SCOPUS:84888367141
SN - 1078-0998
VL - 19
SP - 2547
EP - 2559
JO - Inflammatory bowel diseases
JF - Inflammatory bowel diseases
IS - 12
ER -