Multimodal control of dendritic cell functions by nociceptors

Science, Journal Year: 2023, Volume and Issue: 379(6639)

Published: March 31, 2023

It is known that interactions between nociceptors and dendritic cells (DCs) can modulate immune responses in barrier tissues. However, our understanding of the underlying communication frameworks remains rudimentary. Here, we show control DCs three molecularly distinct ways. First, release calcitonin gene-related peptide imparts a transcriptional profile on steady-state characterized by expression pro-interleukin-1β other genes implicated DC sentinel functions. Second, nociceptor activation induces contact-dependent calcium fluxes membrane depolarization enhances their production proinflammatory cytokines when stimulated. Finally, nociceptor-derived chemokine CCL2 contributes to orchestration DC-dependent local inflammation induction adaptive against skin-acquired antigens. Thus, combined actions chemokines, neuropeptides, electrical activity fine-tune

Language: Английский

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CCL5-producing migratory dendritic cells guide CCR5+ monocytes into the draining lymph nodes

The Journal of Experimental Medicine, Journal Year: 2023, Volume and Issue: 220(6)

Published: March 22, 2023

Dendritic cells (DCs) and monocytes capture, transport, present antigen to cognate T in the draining lymph nodes (LNs) a CCR7-dependent manner. Since only migratory DCs express this chemokine receptor, it is unclear how reach LN. In steady-state following inhalation of several PAMPs, scRNA-seq identified LN mononuclear phagocytes as monocytes, resident, or type 1 2 conventional (c)DCs, despite downregulation Xcr1, Clec9a, H2-Ab1, Sirpa, Clec10a transcripts on cDCs. Migratory cDCs, however, upregulated Ccr7, Ccl17, Ccl22, Ccl5. expressed Ccr5, high-affinity receptor for Using two tracking methods, we observed that both CD88hiCD26lomonocytes CD88−CD26hi cDCs captured inhaled antigens lung migrated LNs. Antigen exposure mixed-chimeric Ccl5-, Ccr2-, Ccr5-, Ccr7-, Batf3-deficient mice demonstrated while antigen-bearing use CCR7 LN, CCR5 follow CCL5-secreting into where they regulate DC-mediated immunity.

Language: Английский

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Dendritic Cell Vaccines: A Shift from Conventional Approach to New Generations

Cells, Journal Year: 2023, Volume and Issue: 12(17), P. 2147 - 2147

Published: Aug. 25, 2023

In the emerging era of cancer immunotherapy, immune checkpoint blockades (ICBs) and adoptive cell transfer therapies (ACTs) have gained significant attention. However, their therapeutic efficacies are limited due to presence cold type tumors, immunosuppressive tumor microenvironment, immune-related side effects. On other hand, dendritic (DC)-based vaccines been suggested as a new immunotherapy regimen that can address limitations encountered by ICBs ACTs. Despite success first generation DC-based vaccines, represented FDA-approved vaccine Provenge, several challenges remain unsolved. Therefore, DC strategies actively investigated. This review addresses currently most adopted classical evaluates generations in detail, including biomaterial-based, immunogenic death-inducing, mRNA-pulsed, small extracellular vesicle (sEV)-based, sEV-based vaccines. These innovative envisioned provide breakthrough landscape expected be supported further preclinical clinical studies.

Language: Английский

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Mature dendritic cells enriched in immunoregulatory molecules (mregDCs): A novel population in the tumour microenvironment and immunotherapy target

Clinical and Translational Medicine, Journal Year: 2023, Volume and Issue: 13(2)

Published: Feb. 1, 2023

Abstract Background Dendritic cells (DCs) mediate divergent immune effects by activating T or negatively regulating the response to promote tolerance. They perform specific functions determined their tissue distribution and maturation state. Traditionally, immature semimature DCs were described have immunosuppressive effects, leading Nonetheless, recent research has demonstrated that mature can also suppress under certain circumstances. Main body Mature enriched in immunoregulatory molecules (mregDCs) emerged as a regulatory module across species tumour types. Indeed, distinct roles of mregDCs immunotherapy sparked interest researchers field single‐cell omics. In particular, these found be associated with positive favourable prognosis. Conclusion Here, we provide general overview latest most notable advances findings regarding basic features complex nonmalignant diseases microenvironment. We emphasise important clinical implications tumours.

Language: Английский

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Therapeutic induction of antigen-specific immune tolerance

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 24(5), P. 338 - 357

Published: Dec. 12, 2023

Language: Английский

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