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Mucosal Immunol ; 11(3): 681-692, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29346347

RESUMO

Antibody responses induced at mucosal and nonmucosal sites demonstrate a significant level of autonomy. Here, we demonstrate a key role for mucosal interferon regulatory factor-4 (IRF4)-dependent CD103+CD11b+ (DP), classical dendritic cells (cDCs) in the induction of T-dependent immunoglobulin G (IgG) and immunoglobulin A (IgA) responses in the mesenteric lymph node (MLN) following systemic immunization with soluble flagellin (sFliC). In contrast, IRF8-dependent CD103+CD11b- (SP) are not required for these responses. The lack of this response correlated with a complete absence of sFliC-specific plasma cells in the MLN, small intestinal lamina propria, and surprisingly also the bone marrow (BM). Many sFliC-specific plasma cells accumulating in the BM of immunized wild-type mice expressed α4ß7+, suggesting a mucosal origin. Collectively, these results suggest that mucosal DP cDC contribute to the generation of the sFliC-specific plasma cell pool in the BM and thus serve as a bridge linking the mucosal and systemic immune system.


Assuntos
Células Dendríticas/imunologia , Fatores Reguladores de Interferon/metabolismo , Linfonodos/imunologia , Mucosa/imunologia , Plasmócitos/imunologia , Animais , Antígenos CD/metabolismo , Antígeno CD11b/metabolismo , Células Cultivadas , Flagelina/imunologia , Imunidade Humoral , Imunoglobulina A/metabolismo , Switching de Imunoglobulina , Imunoglobulina G/metabolismo , Cadeias alfa de Integrinas/metabolismo , Integrina alfa4/metabolismo , Cadeias beta de Integrinas/metabolismo , Fatores Reguladores de Interferon/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
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