RESUMO
Interleukin-22 (IL-22) is mainly produced at barrier surfaces by T cells and innate lymphoid cells and is crucial to maintain epithelial integrity. However, dysregulated IL-22 action leads to deleterious inflammation and is involved in diseases such as psoriasis, intestinal inflammation, and cancer. IL-22 binding protein (IL-22BP) is a soluble inhibitory IL-22 receptor and may represent a crucial regulator of IL-22. We show both in rats and mice that, in the steady state, the main source of IL-22BP is constituted by a subset of conventional dendritic cells (DCs) in lymphoid and non-lymphoid tissues. In mouse intestine, IL-22BP was specifically expressed in lamina propria CD103(+)CD11b(+) DC. In humans, IL-22BP was expressed in immature monocyte-derived DC and strongly induced by retinoic acid but dramatically reduced upon maturation. Our data suggest that a subset of immature DCs may actively participate in the regulation of IL-22 activity in the gut by producing high levels of IL-22BP.
Assuntos
Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Receptores de Interleucina/genética , Tretinoína/farmacologia , Animais , Antígenos CD4/metabolismo , Diferenciação Celular/imunologia , Células Dendríticas/citologia , Células Dendríticas/efeitos dos fármacos , Perfilação da Expressão Gênica , Humanos , Mucosa Intestinal/metabolismo , Intestinos/imunologia , Masculino , Monócitos/citologia , Monócitos/imunologia , Monócitos/metabolismo , Especificidade de Órgãos/genética , Isoformas de Proteínas , Ratos , Receptores de Interleucina/metabolismo , Baço/citologia , Baço/imunologia , Baço/metabolismoRESUMO
Intestinal dendritic cells (DCs) continuously migrate through lymphatics to mesenteric lymph nodes where they initiate immunity or tolerance. Recent research has focused on populations of intestinal DCs expressing CD103. Here we demonstrate, for the first time, the presence of two distinct CD103(-) DC subsets in intestinal lymph. Similar to CD103(+) DCs, these intestine-derived CD103(-) DCs are responsive to Flt3 and they efficiently prime and confer a gut-homing phenotype to naive T cells. However, uniquely among intestinal DCs, CD103(-) CD11b(+) CX(3)CR1(int) lymph DCs induce the differentiation of both interferon-γ and interleukin-17-producing effector T cells, even in the absence of overt stimulation. Priming by CD103(-) CD11b(+) DCs represents a novel mechanism for the rapid generation of effector T-cell responses in the gut. Therefore, these cells may prove to be valuable targets for the treatment of intestinal inflammation or in the development of effective oral vaccines.
