Thymus leukemia antigen controls intraepithelial lymphocyte function and inflammatory bowel disease.
Intestinal intraepithelial lymphocytes (IEL) bear a partially activated phenotype that permits them to rapidly respond to antigenic insults. However, this phenotype also implies that IEL must be highly controlled to prevent misdirected immune reactions. It has been suggested that IEL are regulated through the interaction of the CD8alpha alpha homodimer with the thymus leukemia (TL) antigen expressed by intestinal epithelial cells. We have generated and characterized mice genetically-deficient in TL expression. Our findings show that TL expression has a critical role in maintaining IEL effector functions. Also, TL deficiency accelerated colitis in a genetic model of inflammatory bowel disease. These findings reveal an important regulatory role of TL in controlling IEL function and intestinal inflammation.
Olivares-Villagómez
Danyvid
D
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. danyvid.olivares-villagomez@vanderbilt.edu
Mendez-Fernandez
Yanice V
YV
Parekh
Vrajesh V
VV
Lalani
Saif
S
Vincent
Tiffaney L
TL
Cheroutre
Hilde
H
Van Kaer
Luc
L
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D049109:Cell Proliferation; D003092:Colitis / Q000276:immunology / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004848:Epithelium / Q000276:immunology* / Q000473:pathology; D006706:Homeostasis; D007156:Immunologic Memory; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000473:pathology; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology
D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C028388:thymus-leukemia antigens