The immune system does not merely react — it adapts. Our work investigates how the bone marrow functions as a central sensor, integrating signals from peripheral tissues to configure immune responses across the organism. We aim to define the cellular and molecular mechanisms underlying these inter-organ communication axes, particularly how haematopoiesis is tuned to generate appropriate effector responses, ranging from cytotoxicity to tissue repair.
We focus on conventional dendritic cells (cDCs) because of their central role in orchestrating immunity and their growing clinical relevance in vaccination and cancer immunotherapy. cDCs act as sentinels in all tissues, continuously interpreting the physiological state of the organism and relaying this information to both immune and non-immune compartments to coordinate immunity and tolerance. These cells are short-lived in tissues and are constantly replenished by progenitors originating in the bone marrow.
Our central hypothesis is that cDCs are not solely shaped by local tissue cues, but are pre-configured at the level of their progenitors in the bone marrow. In this view, the bone marrow senses systemic physiological changes and regulates the output and composition of cDC subsets accordingly. Because distinct cDC subsets prime different T cell responses, this upstream control effectively determines the “flavour” of the immune response, influencing whether immunity is geared towards pathogen clearance, tissue repair, or tumour control.
By studying this central sensing axis, we seek to understand how cDC diversity is generated, how functional specialisation is imprinted during development, and how this process can be modulated. Importantly, targeting progenitors in the bone marrow may offer a more durable and system-wide means of shaping immunity compared to acting on short-lived cells in peripheral tissues. This provides a conceptual framework for developing strategies to fine-tune immune responses in vaccination, infection, and cancer.

Our work is supported by the Champalimaud Foundation, a European Research Council Starting Grant (StG 101116335), an EHA Kick-Off Grant (KOG-202409-06691) and a La Caixa Health Grant (HR25-00055).

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