Social influences on delayed gratification in New Caledonian crows and Eurasian jays

Self-control underlies goal-directed behaviour in humans and other animals. Delayed gratification ‐ a measure of self-control ‐ requires the ability to tolerate delays and/or invest more effort to obtain a reward of higher value over one of lower value, such as food or mates. Social context, in particular, the presence of competitors, may influence delayed gratification. We adapted the ‘rotating-tray’ paradigm, where subjects need to forgo an immediate, lower-quality (i.e. less preferred) reward for a delayed, higher-quality (i.e. more preferred) one, to test social influences on delayed gratification in two corvid species: New Caledonian crows and Eurasian jays. We compared choices for immediate vs. delayed rewards while alone, in the presence of a competitive conspecific and in the presence of a non-competitive conspecific. We predicted that, given the increased risk of losing a reward with a competitor present, both species would similarly, flexibly alter their choices in the presence of a conspecific compared to when alone. We found that species differed: jays were more likely to select the immediate, less preferred reward than the crows. We also found that jays were more likely to select the immediate, less preferred reward when a competitor or non-competitor was present than when alone, or when a competitor was present compared to a non-competitor, while the crows selected the delayed, highly preferred reward irrespective of social presence. We discuss our findings in relation to species differences in socio-ecological factors related to adult sociality and food-caching (storing). New Caledonian crows are more socially tolerant and moderate cachers, while Eurasian jays are highly territorial and intense cachers that may have evolved under the social context of cache pilfering and cache protection strategies. Therefore, flexibility (or inflexibility) in delay of gratification under different social contexts may relate to the species’ social tolerance and related risk of competition.</p

Table_4_Transcriptional programming of immunoregulatory responses in human Langerhans cells.csv

Human epidermal Langerhans cells (LCs) maintain immune homeostasis in the skin. To examine transcriptional programming of human primary LCs during homeostasis, we performed scRNA-seq analysis of LCs before and after migration from the epidermis, coupled with functional assessment of their regulatory T cell priming capabilities. The analysis revealed that steady-state LCs exist in a continuum of maturation states and upregulate antigen presentation genes along with an immunoregulatory module including the genes IDO1, LGALS1, LAMTOR1, IL4I, upon their migration. The migration-induced transition in genomic state is accompanied by the ability of LCs to more efficiently prime regulatory T cell responses in co-culture assays. Computational analyses of the scRNAseq datasets using SCENIC and Partial Information Decomposition in Context identified a set of migration-induced transcription factors including IRF4, KLF6 and RelB as key nodes within a immunoregulatory gene regulatory network. These findings support a model in which efficient priming of immunoregulatory responses by LCs is dependent on coordinated upregulation of a migration-coupled maturation program with a immunoregulation-promoting genomic module.</p

Table_6_Transcriptional programming of immunoregulatory responses in human Langerhans cells.csv

Human epidermal Langerhans cells (LCs) maintain immune homeostasis in the skin. To examine transcriptional programming of human primary LCs during homeostasis, we performed scRNA-seq analysis of LCs before and after migration from the epidermis, coupled with functional assessment of their regulatory T cell priming capabilities. The analysis revealed that steady-state LCs exist in a continuum of maturation states and upregulate antigen presentation genes along with an immunoregulatory module including the genes IDO1, LGALS1, LAMTOR1, IL4I, upon their migration. The migration-induced transition in genomic state is accompanied by the ability of LCs to more efficiently prime regulatory T cell responses in co-culture assays. Computational analyses of the scRNAseq datasets using SCENIC and Partial Information Decomposition in Context identified a set of migration-induced transcription factors including IRF4, KLF6 and RelB as key nodes within a immunoregulatory gene regulatory network. These findings support a model in which efficient priming of immunoregulatory responses by LCs is dependent on coordinated upregulation of a migration-coupled maturation program with a immunoregulation-promoting genomic module.</p

Table_5_Transcriptional programming of immunoregulatory responses in human Langerhans cells.csv

Human epidermal Langerhans cells (LCs) maintain immune homeostasis in the skin. To examine transcriptional programming of human primary LCs during homeostasis, we performed scRNA-seq analysis of LCs before and after migration from the epidermis, coupled with functional assessment of their regulatory T cell priming capabilities. The analysis revealed that steady-state LCs exist in a continuum of maturation states and upregulate antigen presentation genes along with an immunoregulatory module including the genes IDO1, LGALS1, LAMTOR1, IL4I, upon their migration. The migration-induced transition in genomic state is accompanied by the ability of LCs to more efficiently prime regulatory T cell responses in co-culture assays. Computational analyses of the scRNAseq datasets using SCENIC and Partial Information Decomposition in Context identified a set of migration-induced transcription factors including IRF4, KLF6 and RelB as key nodes within a immunoregulatory gene regulatory network. These findings support a model in which efficient priming of immunoregulatory responses by LCs is dependent on coordinated upregulation of a migration-coupled maturation program with a immunoregulation-promoting genomic module.</p

DataSheet_1_Transcriptional programming of immunoregulatory responses in human Langerhans cells.pdf

Human epidermal Langerhans cells (LCs) maintain immune homeostasis in the skin. To examine transcriptional programming of human primary LCs during homeostasis, we performed scRNA-seq analysis of LCs before and after migration from the epidermis, coupled with functional assessment of their regulatory T cell priming capabilities. The analysis revealed that steady-state LCs exist in a continuum of maturation states and upregulate antigen presentation genes along with an immunoregulatory module including the genes IDO1, LGALS1, LAMTOR1, IL4I, upon their migration. The migration-induced transition in genomic state is accompanied by the ability of LCs to more efficiently prime regulatory T cell responses in co-culture assays. Computational analyses of the scRNAseq datasets using SCENIC and Partial Information Decomposition in Context identified a set of migration-induced transcription factors including IRF4, KLF6 and RelB as key nodes within a immunoregulatory gene regulatory network. These findings support a model in which efficient priming of immunoregulatory responses by LCs is dependent on coordinated upregulation of a migration-coupled maturation program with a immunoregulation-promoting genomic module.</p

Table_3_Transcriptional programming of immunoregulatory responses in human Langerhans cells.csv

Human epidermal Langerhans cells (LCs) maintain immune homeostasis in the skin. To examine transcriptional programming of human primary LCs during homeostasis, we performed scRNA-seq analysis of LCs before and after migration from the epidermis, coupled with functional assessment of their regulatory T cell priming capabilities. The analysis revealed that steady-state LCs exist in a continuum of maturation states and upregulate antigen presentation genes along with an immunoregulatory module including the genes IDO1, LGALS1, LAMTOR1, IL4I, upon their migration. The migration-induced transition in genomic state is accompanied by the ability of LCs to more efficiently prime regulatory T cell responses in co-culture assays. Computational analyses of the scRNAseq datasets using SCENIC and Partial Information Decomposition in Context identified a set of migration-induced transcription factors including IRF4, KLF6 and RelB as key nodes within a immunoregulatory gene regulatory network. These findings support a model in which efficient priming of immunoregulatory responses by LCs is dependent on coordinated upregulation of a migration-coupled maturation program with a immunoregulation-promoting genomic module.</p

Table_1_Transcriptional programming of immunoregulatory responses in human Langerhans cells.xlsx

Human epidermal Langerhans cells (LCs) maintain immune homeostasis in the skin. To examine transcriptional programming of human primary LCs during homeostasis, we performed scRNA-seq analysis of LCs before and after migration from the epidermis, coupled with functional assessment of their regulatory T cell priming capabilities. The analysis revealed that steady-state LCs exist in a continuum of maturation states and upregulate antigen presentation genes along with an immunoregulatory module including the genes IDO1, LGALS1, LAMTOR1, IL4I, upon their migration. The migration-induced transition in genomic state is accompanied by the ability of LCs to more efficiently prime regulatory T cell responses in co-culture assays. Computational analyses of the scRNAseq datasets using SCENIC and Partial Information Decomposition in Context identified a set of migration-induced transcription factors including IRF4, KLF6 and RelB as key nodes within a immunoregulatory gene regulatory network. These findings support a model in which efficient priming of immunoregulatory responses by LCs is dependent on coordinated upregulation of a migration-coupled maturation program with a immunoregulation-promoting genomic module.</p

Table_2_Transcriptional programming of immunoregulatory responses in human Langerhans cells.csv

Human epidermal Langerhans cells (LCs) maintain immune homeostasis in the skin. To examine transcriptional programming of human primary LCs during homeostasis, we performed scRNA-seq analysis of LCs before and after migration from the epidermis, coupled with functional assessment of their regulatory T cell priming capabilities. The analysis revealed that steady-state LCs exist in a continuum of maturation states and upregulate antigen presentation genes along with an immunoregulatory module including the genes IDO1, LGALS1, LAMTOR1, IL4I, upon their migration. The migration-induced transition in genomic state is accompanied by the ability of LCs to more efficiently prime regulatory T cell responses in co-culture assays. Computational analyses of the scRNAseq datasets using SCENIC and Partial Information Decomposition in Context identified a set of migration-induced transcription factors including IRF4, KLF6 and RelB as key nodes within a immunoregulatory gene regulatory network. These findings support a model in which efficient priming of immunoregulatory responses by LCs is dependent on coordinated upregulation of a migration-coupled maturation program with a immunoregulation-promoting genomic module.</p

Loss of US18 and US20 increases NK degranulation in response to HCMV-infected targets.

<p>A. Fibroblasts (HF-TERTs) were mock infected or infected with the Merlin strain of HCMV or mutants lacking US18 (ΔUS18), US20 (ΔUS20) or combination of US18 and US20 (ΔUS18, ΔUS20) for 72 h. Infected cells were incubated with donor PBMC for 5 h and NK degranulation assessed by % CD107⁺ cells within the CD3⁻, CD56⁺ population by flow cytometry. Results are shown from 3 separate donors performed in triplicate and the mean of pooled results was analysed by Student's t-test (*<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001). B. HF-TERTs were mock infected or infected with the Merlin strain of HCMV or the US18 and US20 deletion mutant for 72 h. Infected cells were incubated with isotype control or a MICA blocking antibody for 30 min prior to incubation with donor PBMC for 5 h. NK degranulation was assessed by % CD107⁺ cells within the CD3⁻, CD56⁺ population by flow cytometry. Results are shown from 2 separate donors performed in triplicate and the results were analysed by Student's t-test (**<i>P</i><0.01, ***<i>P</i><0.001, ns = not significant).</p

US18 and US20 down-regulate MICA levels.

<p>A. Fibroblasts (HF-CARs) were infected with recombinant adenovirus expressing the individual US18–US22 genes for 72 h. Hydrophobic proteins were extracted using Triton X-114 and protein expression analyzed by immunoblotting. Data shown is representative of four similar independent experiments. B. Fibroblasts (HF-TERTs) were mock infected or infected with HCMV, ΔUS18, ΔUS20, ΔUS18&20 for 72 h. Hydrophobic proteins were extracted using Triton X-114, mock-treated (-) or treated with either Endoglycosidase H (E) or PNGase F (P) and protein expression analyzed by immunoblotting. Results are representative of two independent experiments. C. Fibroblasts (HF-TERTs) were mock infected or infected with HCMV, ΔUS18 or ΔUS18, ΔUS20 for 72 h. Cell surface expression was analyzed by immunostaining and flow cytometry. Results shown are the median fluorescence intensity (MFI) and are from four independent experiments. The mean of the results was analysed by Student's t-test (*<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001). <i>D.</i> Dermal fibroblasts expressing different MICA alleles were mock infected or infected with HCMV, ΔUS18 or ΔUS18, ΔUS20 for 72 h. Cell surface expression was analyzed by immunostaining and flow cytometry. Results shown are the median fluorescence intensity (MFI) and are from three independent experiments. The mean of the results was analysed by Student's t-test (*<i>P</i><0.05, **<i>P</i><0.01, ns = not significant).</p