Anti-T-cell Ig and mucin domain-containing protein 1 antibody decreases TH2 airway inflammation in a mouse model of asthma.
BACKGROUND
The T-cell Ig and mucin domain-containing (TIM) gene locus has been linked to differences in T(H)2 responsiveness and asthma susceptibility in mice. The homologous locus in human subjects harbors the gene for TIM-1, which encodes a receptor for hepatitis A virus and has been linked with decreased susceptibility to atopic disease in hepatitis A virus-seropositive individuals.


OBJECTIVE
We investigated the effects of administering antibodies against TIM-1 in a mouse model of allergic asthma to determine whether the treatment could downregulate T(H)2 cytokines and reduce pulmonary inflammation.


METHODS
BALB/c mice were sensitized and challenged with ovalbumin to induce airway inflammation. Before the ovalbumin challenge, mice were treated with anti-TIM-1 mAb or a control antibody.


RESULTS
Administration of anti-TIM-1 antibody to mice after ovalbumin sensitization and before ovalbumin challenge results in a significant decrease in inflammatory cells in bronchoalveolar lavage fluid compared with administration of a control antibody. The decrease is accompanied by significantly lower antigen-specific production of the T(H)2 cytokines IL-10 and IL-13 by cells from the draining lymph nodes. The T(H)1 cytokine IFN-gamma appears to be unaffected. Analysis of the lungs shows that goblet cell hyperplasia and mucus production and the expression of IL-10 are markedly decreased in anti-TIM-1-treated mice.


CONCLUSIONS
The results indicate that anti-TIM-1 might offer a novel approach to treating asthma.
Encinas
Jeffrey A
JA
Telos Pharmaceuticals LLC, San Diego, California 92131, USA. jencinas@forestlifesciences.com
Janssen
Edith M
EM
Weiner
David B
DB
Calarota
Sandra A
SA
Nieto
Daisy
D
Moll
Thomas
T
Carlo
Dennis J
DJ
Moss
Ronald B
RB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001249:Asthma / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D000072596:Hepatitis A Virus Cellular Receptor 1; D007249:Inflammation / Q000517:prevention & control*; D016753:Interleukin-10 / Q000096:biosynthesis; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016207:Cytokines; C442240:Havcr1 protein, mouse; D000072596:Hepatitis A Virus Cellular Receptor 1; D008565:Membrane Proteins; D016753:Interleukin-10