There are three major dendritic cell (DC) subsets in both humans and mice, that is, plasmacytoid DCs and two types of conventional DCs (cDCs), cDC1s and cDC2s. cDC2s are important for polarizing CD4 naive T cells into different subsets, including Th1, Th2, Th17, Th22, and regulatory T cells. In mice, cDC2s can be further divided into phenotypically and functionally distinct subgroups. However, subsets of human cDC2s have not been reported. In the present study, we showed that human blood CD1c cDCs (cDC2s) can be further separated into two subpopulations according to their CD5 expression status. Comparative transcriptome analyses showed that the CD5 DCs expressed higher levels of cDC2-specific genes, including IFN regulatory factor 4, which is essential for the cDC2 development and its migration to lymph nodes. In contrast, CD5 DCs preferentially expressed monocyte-related genes, including the lineage-specific transcription factor MAFB. Furthermore, compared with the CD5 subpopulation, the CD5 subpopulation showed stronger migration toward CCL21 and overrepresentation among migratory DCs in lymph nodes. Additionally, the CD5 DCs induced naive T cell proliferation more potently than did the CD5 DCs. Moreover, CD5 DCs induced higher levels of IL-10-, IL-22-, and IL-4-producing T cell formation, whereas CD5 DCs induced higher levels of IFN-γ-producing T cell formation. Thus, we show that human blood CD1c cDC2s encompass two subsets that differ significantly in phenotype, that is, gene expression and functions. We propose that these two subsets of human cDC2s could potentially play contrasting roles in immunity or tolerance.
The ability to modulate sensitivity in sensory systems is essential for useful information to be extracted from fluctuating stimuli in a wide range of background conditions. The mechanisms underlying sensitivity regulation in insect primary olfactory neurons are poorly understood. Here we reveal that dephosphorylation of Orco that occurs upon prolonged odor exposure is a mechanism underlying reduction in odorant sensitivity in primary olfactory neurons in both sexes. mutants, unable to phosphorylate this position, have low intrinsic odorant sensitivity that is independent of altered expression or localization. A phosphomimetic allele, , has enhanced odorant sensitivity compared with wild-type controls. To explore the functional ramifications of this phosphorylation, we generated phospho-specific antiserum to Orco and show that phosphorylation at this residue is dynamically regulated by odorant exposure with concomitant modulation of odorant sensitivity. Orco is phosphorylated in the sensitized state, and odorant exposure triggers dephosphorylation and desensitization without altering receptor localization. We further show that dephosphorylation of Orco is triggered by neuronal activity, and not conformational changes in the receptor occurring upon ligand binding. Mutant flies unable to regulate Orco function through phosphorylation at S289 are defective for odor-guided behavior. These findings provide insight into the mechanisms underlying regulation of insect odorant receptors We have uncovered a mechanism underlying olfactory receptor sensitivity regulation in The phosphorylation state of Orco is altered in an odorant-dependent manner and changes in phosphorylation affect receptor sensitivity without changing subcellular localization. We show that neuronal activity triggers the phosphorylation changes and that this phenomenon is important for odorant-guided behaviors in This phosphorylation site is conserved in other insects, including mosquitoes, indicating this mechanism may be a target for manipulation of insect behaviors in the future.
Chemosensory proteins (CSPs) are soluble proteins found only in arthropods. Some of them fill the lumen of chemosensilla and are believed to play a role similar to that of odorant-binding proteins in the detection of semiochemicals. Other members of the CSP family have been reported to perform different functions, from delivery of pheromones to development. This report is focused on a member (CSP4) of the family that is highly and almost exclusively present in the proboscis of two sibling noctuid species, Helicoverpa armigera and H. assulta. We expressed the protein in bacteria and measured binding to terpenoids and related compounds. Using specific antibodies, we found that when the moths suck on a sugar solution, CSP4 is partly extruded from the proboscis. A solution of protein can also fill a hydrophobic tube of same length and diameter as the proboscis by capillary action. On this basis, we suggest that CSP4 acts as a wetting agent to reduce the surface tension of aqueous solutions and consequently the pressure involved in sucking.
Two sympatric species Helicoverpa armigera and Helicoverpa assulta use (Z)-11-hexadecenal and (Z)-9-hexadecenal as sex pheromone components in reverse ratio. They also share several other pheromone gland components (PGCs). We present a comparative study on the olfactory coding mechanism and behavioral effects of these additional PGCs in pheromone communication of the two species using single sensillum recording, in situ hybridization, calcium imaging, and wind tunnel. We classify antennal sensilla types A, B and C into A, B1, B2, C1, C2 and C3 based on the response profiles, and identify the glomeruli responsible for antagonist detection in both species. The abundance of these sensilla types when compared with the number of OSNs expressing each of six pheromone receptors suggests that HarmOR13 and HassOR13 are expressed in OSNs housed within A type sensilla, HarmOR14b within B and C type sensilla, while HassOR6 and HassOR16 within some of C type sensilla. We find that for H. armigera, (Z)-11-hexadecenol and (Z)-11-hexadecenyl acetate act as behavioral antagonists. For H. assulta, instead, (Z)-11-hexadecenyl acetate acts as an agonist, while (Z)-9-hexadecenol, (Z)-11-hexadecenol and (Z)-9-hexadecenyl acetate are antagonists. The results provide an overall picture of intra- and interspecific olfactory and behavioral responses to all PGCs in two sister species.
While exercise has been shown to reduce the negative effects of substance withdrawal symptoms, no research has investigated if Tai Chi, a traditional Chinese exercise, has similar effects. Here, we observed the physiological effects of Tai Chi on protracted abstinence syndrome (PAS) in female heroin addicts by comprehensively inspecting their immune system function, complete blood count, hepatic function and renal function. To determine the psychological effects, we used the Hamilton Rating Scale for Depression (HRSD) and the rating scale of heroin withdrawal symptoms. We recruited 70 heroin-addicted young women beginning to undergo withdrawal and randomly assigned them into two groups: one group received one-hour Tai Chi exercise every two days (Tai Chi group, n = 36) and the other group did not (control group, n = 34). Thirty-three patients finished this six-month trial. Numerous significant physiological differences were observed between all heroin-addicted subjects (n = 70) and age-matched healthy individuals (n = 18), suggesting a deleterious effect of drug addiction. There were improvements for certain physical parameters between the Tai Chi group (n = 17) and the control group (n = 16), although the differences were not statistically significant. We observed a small significant difference in psychological effects near the 60-day mark between the two groups. Taken together, our results suggest that Tai Chi might have a positive effect on PAS, which future studies can confirm by using an expanded sample size, longer trial time, and more sensitive and specific indicators of psychological and physiological health.
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