title: Roles of T cell-associated L-selectin and β7 integrins during induction and regulation of chronic colitis.
abstract: BACKGROUND
  L-selectin (CD62L) and β(7) 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 β(7) 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 β(7)(-/-) single-deficient T cells induced moderate to severe disease with slightly different kinetics. However, transfer of CD62L(-/-) β(7)(-/-) 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 wild-type T cells.
  
  
  CONCLUSIONS
  We established that T cells can use either CD62L(-/-) or β(7)(-/-) integrins to induce chronic colitis, but lack of both abrogates their colitogenic potential. Effector T cells critically rely on β(7) 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.
authors.affiliation: *Center of Excellence for Arthritis and Rheumatology, Louisiana State University Health Sciences Center, Shreveport, Louisiana; †Division of Gastroenterology and Hepatology, Department of Medicine, Louisiana State University Health Sciences Center, Shreveport, Louisiana; and ‡Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, Louisiana.
authors.forename: Elvira
authors.initials: E
authors.lastname: Kurmaeva
authors.forename: Moheb
authors.initials: M
authors.lastname: Boktor
authors.forename: Songling
authors.initials: S
authors.lastname: Zhang
authors.forename: Richard
authors.initials: R
authors.lastname: Bao
authors.forename: Seth
authors.initials: S
authors.lastname: Berney
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Ostanin
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002908:Chronic Disease; D003092:Colitis / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D041981:Gastrointestinal Tract / Q000378:metabolism* / Q000473:pathology; D018398:Homeodomain Proteins / Q000502:physiology; D039641:Integrin beta Chains / Q000502:physiology*; D019041:L-Selectin / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D016207:Cytokines; D018398:Homeodomain Proteins; D039641:Integrin beta Chains; C091368:integrin beta7; D019041:L-Selectin; C064658:RAG-1 protein