Your browser doesn't support javascript.
loading
TLR-induced local metabolism of vitamin D3 plays an important role in the diversification of adaptive immune responses.
J Immunol ; 182(7): 4296-305, 2009 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-19299729
ABSTRACT
The addition of monophosphoryl lipid A, a minimally toxic derivative of LPS, to nonmucosally administered vaccines induced both systemic and mucosal immune responses to coadministered Ags. This was dependent on an up-regulated expression of 1alpha-hydroxylase (CYP27B1, 1alphaOHase), the enzyme that converts 25-hydroxycholecalciferol, a circulating inactive metabolite of vitamin D(3), into 1,25(OH)2D(3) (calcitriol). In response to locally produced calcitriol, myeloid dendritic cells (DCs) migrated from cutaneous vaccination sites into multiple secondary lymphoid organs, including classical inductive sites of mucosal immunity, where they effectively stimulated B and T cell immune responses. The endogenous production of calcitriol by monophosphoryl lipid A-stimulated DCs appeared to be Toll-IL-1R domain-containing adapter-inducing IFN-beta-dependent, mediated through a type 1 IFN-induced expression of 1alphaOHase. Responsiveness to calcitriol was essential to promote the trafficking of mobilized DCs to nondraining lymphoid organs. Collectively, these studies help to expand our understanding of the physiologically important roles played by locally metabolized vitamin D(3) in the initiation and diversification of adaptive immune responses. The influences of locally produced calcitriol on the migration of activated DCs from sites of vaccination/infection into both draining and nondraining lymphoid organs create a condition whereby Ag-responsive B and T cells residing in multiple lymphoid organs are able to simultaneously engage in the induction of adaptive immune responses to peripherally administered Ags as if they were responding to an infection of peripheral or mucosal tissues they were designed to protect.
Assuntos

Similares

MEDLINE

...
LILACS

LIS

Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Células Dendríticas / Vacinas / Adjuvantes Imunológicos / Colecalciferol / Receptores Toll-Like Limite: Animais Idioma: Inglês Revista: J Immunol Ano de publicação: 2009 Tipo de documento: Artigo País de afiliação: Estados Unidos