Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet.
Human asthma is associated with airway infiltration by T helper 2 (TH2) lymphocytes. We observed reduced expression of the TH1 transcription factor, T-bet, in T cells from airways of patients with asthma compared with that in T cells from airways of nonasthmatic patients, suggesting that loss of T-bet might be associated with asthma. Mice with a targeted deletion of the T-bet gene and severe combined immunodeficient mice receiving CD4+ cells from T-bet knockout mice spontaneously demonstrated multiple physiological and inflammatory features characteristic of asthma. Thus, T-bet deficiency, in the absence of allergen exposure, induces a murine phenotype reminiscent of both acute and chronic human asthma.
Finotto
Susetta
S
Critical Care and Pulmonary Division, Division of Gastroenterology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Neurath
Markus F
MF
Glickman
Jonathan N
JN
Qin
Shixin
S
Lehr
Hans A
HA
Green
Francis H Y
FH
Ackerman
Kate
K
Haley
Kathleen
K
Galle
Peter R
PR
Szabo
Susanne J
SJ
Drazen
Jeffrey M
JM
De Sanctis
George T
GT
Glimcher
Laurie H
LH
D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D024061:Collagen Type III / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018390:Gene Targeting; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D020825:T-Box Domain Proteins; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D000098815:T-bet Transcription Factor
D000485:Allergens; D024061:Collagen Type III; D016207:Cytokines; D015848:Interleukin-5; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D015847:Interleukin-4