RESUMO
Nose-associated lymphoid tissue (NALT) in the rodent upper respiratory tract develops postnatally and is considered to be independent of several factors known to be involved in the organogenesis of LN and Peyer's patches (PP). In this study we demonstrate that at least two different pathways result in NALT development. Following NALT anlage formation the intrinsic pathway relies on a signaling cascade including those mediated through the chemokine receptor CXCR5 and the lymphotoxin beta receptor (LTbetaR). This allows for the formation of high endothelial venules and thereby the recruitment of lymphocytes into NALT. Alternatively, high endothelial venule formation and lymphocyte recruitment can be induced in the NALT anlage by environmental signals, which are independent of LT-betaR and chemokine receptor CXCR5 signaling but in part rely on CD40 ligand. Thus, our study identifies a novel mechanism that facilitates the rescue of NALT development at late stages in adult life independent of the canonical LTbetaR-CXCR5 signaling axis.
Assuntos
Antígenos/imunologia , Tecido Linfoide/crescimento & desenvolvimento , Receptor beta de Linfotoxina/fisiologia , Mucosa Nasal/crescimento & desenvolvimento , Receptores CXCR5/fisiologia , Transdução de Sinais/imunologia , Transferência Adotiva , Envelhecimento/imunologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Antígenos de Superfície/metabolismo , Linfócitos B/imunologia , Ligante de CD40/imunologia , Moléculas de Adesão Celular/metabolismo , Contagem de Células , Movimento Celular/imunologia , Vida Livre de Germes/imunologia , Linfonodos/citologia , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Linfócitos/citologia , Tecido Linfoide/irrigação sanguínea , Tecido Linfoide/patologia , Linfotoxina-alfa/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Mutantes , Mucoproteínas , Mucosa Nasal/irrigação sanguínea , Mucosa Nasal/patologia , Propionibacterium acnes/imunologia , Baço/citologia , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/antagonistas & inibidores , Vênulas/crescimento & desenvolvimento , Vênulas/metabolismo , Vênulas/patologiaRESUMO
Allergic airway diseases such as asthma are caused by a failure of the immune system to induce tolerance against environmental Ags. The underlying molecular and cellular mechanisms that initiate tolerance are only partly understood. In this study, we demonstrated that a CCR7-dependent migration of both CD103+ and CD103- lung dendritic cells (DC) to the bronchial lymph node (brLN) is indispensable for this process. Although inhaled Ag is amply present in the brLN of CCR7-deficient mice, T cells cannot be tolerized because of the impaired migration of Ag-carrying DC and subsequent transport of Ag from the lung to the draining lymph node. Consequently, the repeated inhalation of Ag protects wild-type but not CCR7-deficient mice from developing allergic airway diseases. Thus, the continuous DC-mediated transport of inhaled Ag to the brLN is critical for the induction of tolerance to innocuous Ags.
