RESUMEN
Intestinal IL-17-producing cells, including Th17, γ/δ T, and innate lymphoid cells, are differentially distributed along the gastrointestinal tract. In this study, we show that the gut IL-17-producing γ/δ T (γ/δ T17) cells develop before birth and persist in the tissue as long-lived cells with minimal turnover. Most colon γ/δ T17 cells express, together with Vγ4 and CCR6, the scavenger receptor 2 and are mainly restricted to innate lymphoid follicles in the colon. Colon γ/δ T cells in mice that lack conventional dendritic cells 2 produced increased amounts of IL-17 with concomitant heightened epithelial antimicrobial response, such as the C-type lectins Reg3γ and Reg3ß. In the absence of γ/δ T cells or after IL-17 neutralization, this epithelial response was dramatically reduced, underlining the protective role of this unique subpopulation of innate γ/δ T17 cells in the colonic mucosa.
Asunto(s)
Antiinfecciosos/metabolismo , Colon/inmunología , Células Epiteliales/inmunología , Mucosa Intestinal/inmunología , Proteínas Asociadas a Pancreatitis/metabolismo , Linfocitos T/inmunología , Animales , Diferenciación Celular , Células Cultivadas , Desarrollo Fetal , Inmunidad Innata , Interleucina-17/metabolismo , Activación de Linfocitos , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Receptores CCR6/metabolismo , Receptores Depuradores/metabolismoRESUMEN
Circulating CCR2+ monocytes are crucial for maintaining the adult tissue-resident F4/80hiMHCIIhi macrophage pool in the intestinal lamina propria. Here we show that a subpopulation of CCR2-independent F4/80hiMHCIIlow macrophages, which are the most abundant F4/80hi cells in neonates, gradually decline in number in adulthood; these macrophages likely represent the fetal contribution to F4/80hi cells. In colon adenomas of ApcMin/+ mice, F4/80hiMHCIIlow macrophages are not only preserved, but become the dominant subpopulation among tumour-resident macrophages during tumour progression. Furthermore, these pro-tumoural F4/80hiMHCIIlow and F4/80hiMHCIIhi macrophages can self-renew in the tumour and maintain their numbers mostly independent from bone marrow contribution. Analyses of colon adenomas indicate that CSF1 may be a key facilitator of macrophage self-renewal. In summary, the tumour microenvironment creates an isolated niche for tissue-resident macrophages that favours macrophage survival and self-renewal.
Asunto(s)
Adenoma/inmunología , Autorrenovación de las Células , Neoplasias del Colon/inmunología , Pólipos del Colon/inmunología , Macrófagos/citología , Nicho de Células Madre , Microambiente Tumoral , Adenoma/genética , Proteína de la Poliposis Adenomatosa del Colon/genética , Animales , Antígenos de Diferenciación , Supervivencia Celular , Neoplasias del Colon/genética , Pólipos del Colon/genética , Antígenos de Histocompatibilidad Clase II , Factor Estimulante de Colonias de Macrófagos , Ratones , Ratones Noqueados , Ratones Transgénicos , Neoplasias Experimentales , Receptores CCR2/genéticaRESUMEN
Dendritic cells (DCs) and macrophages (MÏs) share close developmental pathways and functional features, leading to blurring of the boundaries between these two cell lineages. However, a deeper understanding of DC and MÏ ontogeny and more refined phenotypic and functional characterizations have helped to delineate pre-DC-derived conventional DCs (cDCs), including cDC1s and cDC2s, from monocyte-derived MÏs. Here, we further refine DC/MÏ cell classification and report that classically defined cDC2s contain a discrete population of monocyte-derived migratory antigen-presenting cells with MÏ phenotype but functional DC features, including cross-presentation.