Inhibition of Th2 adaptive immune responses and pulmonary inflammation by leukocyte Ig-like receptor B4 on dendritic cells.
J Immunol
; 184(2): 1003-13, 2010 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-19966208
ABSTRACT
We previously established that the inhibitory receptor LILRB4 mitigates LPS-induced, neutrophil-dependent pathologic effector mechanisms in inflammation. We now report that LILRB4 on dendritic cells (DCs) counterregulates development of an adaptive Th2 immune response and ensuing inflammation in a model of allergic pulmonary inflammation, initiated by inhalation sensitization with OVA and LPS followed by airway challenge with OVA. We found that Lilrb4(-/-) mice had significantly exacerbated eosinophilic pulmonary inflammation, as assessed in bronchoalveolar lavage and lung tissue, as well as elevated levels of OVA-specific IgE and Th2 cytokines produced by OVA-restimulated lymph node cells. LILRB4 was preferentially expressed on MHC class II(high)CD86(high) OVA-bearing DCs in lung-draining lymph nodes after sensitization or challenge. Moreover, the lymph nodes of Lilrb4(-/-) mice had significantly more of these mature DCs after challenge with OVA, which was accompanied by significantly more IL-4-producing lymphocytes, compared with Lilrb4(+/+) mice. Sensitization of naive Lilrb4(+/+) mice by transfer of OVA-LPS-pulsed Lilrb4(-/-) bone marrow-derived DCs was sufficient to confer exacerbated allergic lung pathology upon challenge with OVA, compared with mice that received Lilrb4(+/+) bone marrow-derived DCs. Our findings establish that maturation and migration of pulmonary DCs to lymph nodes in response to Ag and an innate immune stimulus is associated with upregulated expression of LILRB4. In addition, this receptor attenuates the number of these mature DCs and attendant IL-4-producing lymphocytes in the lymph nodes, and accordingly, the ability of DCs to elicit pathologic Th2 pulmonary inflammation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pneumonia
/
Células Dendríticas
/
Glicoproteínas de Membrana
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Receptores Imunológicos
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Células Th2
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Imunidade Adaptativa
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article