IL-13 regulates the immune response to inhaled antigens.
The large inhibitory effect of IL-13 blockers on the asthma phenotype prompted us to ask whether IL-13 would play a role in regulating the allergic immune response in addition to its documented effects on structural pulmonary cells. Because IL-13 does not interact with murine T or B cells, but with monocytes, macrophages, and dendritic cells (DCs), we examined the role of IL-13 in the activation of pulmonary macrophages and DCs and in the priming of an immune response to a harmless, inhaled Ag. We found that a majority of cells called "alveolar or interstitial macrophages" express CD11c at high levels (CD11c(high)) and are a mixture of at least two cell types as follows: 1) cells of a mixed phenotype expressing DC and macrophage markers (CD11c, CD205, and F4/80) but little MHC class II (MHC II); and 2) DC-like cells expressing CD11c, CD205, MHC II, and costimulatory molecules. Endogenous IL-13 was necessary to induce and sustain the increase in MHC II and CD40 expression by pulmonary CD11c(high) cells, demonstrated by giving an IL-13 inhibitor as a measure of prevention or reversal to allergen-primed and -challenged mice. Conversely, IL-13 given by inhalation to naive mice increased the expression of MHC II and costimulatory molecules by CD11c(high) cells in an IL-4Ralpha-dependent manner. We found that exogenous IL-13 exaggerated the immune and inflammatory responses to an inhaled, harmless Ag, whereas endogenous IL-13 was necessary for the priming of naive mice with an inhaled, harmless Ag. These data indicate that blockade of IL-13 may have therapeutic potential for controlling the immune response to inhaled Ags.
Padilla
Jocelyn
J
James P. Mara Center for Lung Diseases, St. Luke's Roosevelt Hospital and Department of Pathology, Columbia University, New York, NY 10019, USA.
Daley
Eleen
E
Chow
Anthony
A
Robinson
Kesha
K
Parthasarathi
Kaushik
K
McKenzie
Andrew N J
AN
Tschernig
Thomas
T
Kurup
Viswanath P
VP
Donaldson
Debra D
DD
Grunig
Gabriele
G
D000280:Administration, Inhalation; D000281:Administration, Intranasal; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology*; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D039521:CD11c Antigen / Q000096:biosynthesis; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000502:physiology; D018793:Interleukin-13 / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
D000485:Allergens; D000941:Antigens; D039521:CD11c Antigen; D018836:Inflammation Mediators; D018793:Interleukin-13; D010047:Ovalbumin