Pulmonary CD103(+) dendritic cells prime Th2 responses to inhaled allergens.
Allergic asthma stems largely from the actions of T helper 2 (Th2) cells, but the pathways that initiate Th2 responses to inhaled allergens are not fully understood. In the lung, there are two major subsets of dendritic cells (DCs), displaying CD11b or CD103. We found that after taking up inhaled ovalbumin in vivo, purified CD103(+) DCs from the lung or lung-draining lymph nodes primed Th2 differentiation ex vivo. Th2 induction by CD103(+) DCs was also seen when cockroach or house dust mite allergens were used. In contrast, CD11b(hi) DCs primed Th1 differentiation. Moreover, mice lacking CD103(+) DCs displayed diminished Th2 priming to various inhaled allergens and did not develop asthma-like responses following subsequent allergen challenge. Low-level antigen presentation by CD103(+) DCs was necessary, but not sufficient for Th2 priming. Together, these findings show that CD103(+) DCs have a significant role in priming Th2 responses to inhaled allergens.
Laboratory of Respiratory Biology, Division of Intramural Research, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, USA.
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Nakano
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Free
G S
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Whitehead
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Maruoka
R H
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Wilson
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K
Nakano
D N
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Cook
D000280:Administration, Inhalation; D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001249:Asthma / Q000139:chemically induced / Q000276:immunology*; D039481:CD11b Antigen / Q000378:metabolism; D002478:Cells, Cultured; D003058:Cockroaches / Q000276:immunology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D039001:Integrin alpha Chains / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage; D039981:Pyroglyphidae; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D000485:Allergens; D015703:Antigens, CD; D039481:CD11b Antigen; D039001:Integrin alpha Chains; C091367:alpha E integrins; D010047:Ovalbumin