IL-10-treated dendritic cells decrease airway hyperresponsiveness and airway inflammation in mice.
BACKGROUND
IL-10 affects dendritic cell (DC) function, but the effects on airway hyperresponsiveness (AHR) and inflammation are not defined.


OBJECTIVE
We sought to determine the importance of IL-10 in regulating DC function in allergen-induced AHR and airway inflammation.


METHODS
DCs were generated from bone marrow in the presence or absence of IL-10. In vivo IL-10-treated DCs from IL-10(+/+) and IL-10(-/-) donors pulsed with ovalbumin (OVA) were transferred to naive or sensitized mice before challenge. In recipient mice AHR, cytokine levels, cell composition of bronchoalveolar lavage (BAL) fluid, and lung histology were monitored.


RESULTS
In vitro, IL-10-treated DCs expressed lower levels of CD11c, CD80, and CD86; expressed lower levels of IL-12; and suppressed T(H)2 cytokine production. In vivo, after transfer of OVA-pulsed IL-10-treated DCs, naive mice did not have AHR, airway eosinophilia, T(H)2 cytokine increase in BAL fluid, or goblet cell metaplasia when challenged, and in sensitized and challenged mice IL-10-treated DCs suppressed these responses. Levels of IL-10 in BAL fluid and numbers of lung CD4(+)IL-10(+) T cells were increased in mice that received OVA-pulsed IL-10-treated DCs. Transfer of IL-10-treated DCs from IL-10-deficient mice were ineffective in suppressing the responses in sensitized and challenged mice.


CONCLUSIONS
These data demonstrate that IL-10-treated DCs are potent suppressors of the development of AHR, inflammation, and T(H)2 cytokine production; these regulatory functions are at least in part through the induction of endogenous (DC) production of IL-10.


CONCLUSIONS
Modification of DC function by IL-10 can attenuate lung allergic responses, including the development of AHR.
Koya
Toshiyuki
T
Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Matsuda
Hiroyuki
H
Takeda
Katsuyuki
K
Matsubara
Shigeki
S
Miyahara
Nobuaki
N
Balhorn
Annette
A
Dakhama
Azzeddine
A
Gelfand
Erwin W
EW
D019264:Adoptive Transfer; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology*; D016753:Interleukin-10 / Q000378:metabolism*; D051379:Mice; D010047:Ovalbumin / Q000276:immunology
D016207:Cytokines; D016753:Interleukin-10; D010047:Ovalbumin