Novel Cre-Expressing Mouse Strains Permitting to Selectively Track and Edit Type 1 Conventional Dendritic Cells Facilitate Disentangling Their Complexity in vivo.

Type 1 conventional DCs (cDC1) excel in the cross-priming of CD8+ T cells, which is crucial for orchestrating efficient immune responses against viruses or tumors. However, our understanding of their physiological functions and molecular regulation has been limited by the lack of proper mutant mouse models allowing their conditional genetic targeting. Because the Xcr1 and A530099j19rik (Karma/Gpr141b) genes belong to the core transcriptomic fingerprint of mouse cDC1, we used them to engineer two novel Cre-driver lines, the Xcr1Cre and KarmaCre mice, by knocking in an IRES-Cre expression cassette into their 3'-UTR. We used genetic tracing to characterize the specificity and efficiency of these new models in several lymphoid and non-lymphoid tissues, and compared them to the Clec9aCre mouse model, which targets the immediate precursors of cDCs. Amongst the three Cre-driver mouse models examined, the Xcr1Cre model was the most efficient and specific for the fate mapping of all cDC1, regardless of the tissues examined. The KarmaCre model was rather specific for cDC1 when compared with the Clec9aCre mouse, but less efficient than the Xcr1Cre model. Unexpectedly, the Xcr1Cre model targeted a small fraction of CD4+ T cells, and the KarmaCre model a significant proportion of mast cells in the skin. Importantly, the targeting specificity of these two mouse models was not changed upon inflammation. A high frequency of germline recombination was observed solely in the Xcr1Cre mouse model when both the Cre and the floxed alleles were brought by the same gamete irrespective of its gender. Xcr1, Karma, and Clec9a being differentially expressed within the cDC1 population, the three CRE-driver lines examined showed distinct recombination patterns in cDC1 phenotypic subsets. This advances our understanding of cDC1 subset heterogeneity and the differentiation trajectory of these cells. Therefore, to the best of our knowledge, upon informed use, the Xcr1Cre and KarmaCre mouse models represent the best tools currently reported to specifically and faithfully target cDC1 in vivo, both at steady state and upon inflammation. Future use of these mutant mouse models will undoubtedly boost our understanding of the biology of cDC1.

Evaluación de la relación entre el habito y frecuencia del consumo de lácteos y el nivel de calcio presente en la orina de jóvenes universitarios de la ciudad de Armenia / Evaluation of the relationship between the habit and frequency of consumption of milk and calcium this level in urine of college students of the city of Armenia

La presente investigación evaluó los estilos de vida de jóvenes universitarios,en este caso la relación entre el hábito y frecuencia del consumo de lácteosy nivel de calcio presente en la orina de jóvenes entre los 18 y 25 años de laciudad de Armenia. Se realizó un estudio exploratorio descriptivo, en 98jóvenes a los cuales se les aplico un instrumento de valoración donde seobtuvo información acerca de sus estilos de vida, consumo de lácteos, y seles práctico un examen de calcio en orina ocasional. Los resultados obtenidos arrojaron que toda la población objeto de estudio consumen productos lácteos, los hombres prefieren consumir más la leche con un 60% que las mujeres con un 51%. No se encontró correlación entre el consumo de lácteos y la cantidad de calcio presente en la Orina dado que los valores dieron muy cercanos a cero (-0,0288035 - 0,12558183). No se evidenció correlación entre el consumo, frecuencia y tipo de producto lácteo consumido vs. cantidad de calcio encontrada en la orina y la alteración de los niveles de calcio en orina que darían origen al padecimiento de hipercalciuria o hipocalciuria, por lo cual es necesario buscar y correlacionar otras fuentes de calcio que eviten los padecimientos anteriormente mencionados...

XCR1+ dendritic cells promote memory CD8+ T cell recall upon secondary infections with Listeria monocytogenes or certain viruses.

Naive CD8(+) T cell priming during tumor development or many primary infections requires cross-presentation by XCR1(+) dendritic cells (DCs). Memory CD8(+) T lymphocytes (mCTLs) harbor a lower activation threshold as compared with naive cells. However, whether their recall responses depend on XCR1(+) DCs is unknown. By using a new mouse model allowing fluorescent tracking and conditional depletion of XCR1(+) DCs, we demonstrate a differential requirement of these cells for mCTL recall during secondary infections by different pathogens. XCR1(+) DCs were instrumental to promote this function upon secondary challenges with Listeria monocytogenes, vesicular stomatitis virus, or Vaccinia virus, but dispensable in the case of mouse cytomegalovirus. We deciphered how XCR1(+) DCs promote mCTL recall upon secondary infections with Listeria. By visualizing for the first time the in vivo choreography of XCR1(+) DCs, NK cells and mCTLs during secondary immune responses, and by neutralizing in vivo candidate molecules, we demonstrate that, very early after infection, mCTLs are activated, and attracted in a CXCR3-dependent manner, by NK cell-boosted, IL-12-, and CXCL9-producing XCR1(+) DCs. Hence, depending on the infectious agent, strong recall of mCTLs during secondary challenges can require cytokine- and chemokine-dependent cross-talk with XCR1(+) DCs and NK cells.

Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin.

In the skin, the lack of markers permitting the unambiguous identification of macrophages and of conventional and monocyte-derived dendritic cells (DCs) complicates understanding of their contribution to skin integrity and to immune responses. By combining CD64 and CCR2 staining, we successfully identified each of these cell types and studied their origin, transcriptomic signatures, and migratory and T cell stimulatory properties. We also analyzed the impact of microbiota on their development and their contribution to skin inflammation during contact hypersensitivity. Dermal macrophages had a unique scavenging role and were unable to migrate and activate T cells. Conventional dermal DCs excelled both at migrating and activating T cells. In the steady-state dermis, monocyte-derived DCs are continuously generated by extravasated Ly-6C(hi) monocytes. Their T cell stimulatory capacity combined with their poor migratory ability made them particularly suited to activate skin-tropic T cells. Therefore, a high degree of functional specialization occurs among the mononuclear phagocytes of the skin.