Biology subjects

Bartolini, R.

Publications and source records attributed to Bartolini, R..

4 recordsLinked to original sources

bioRxiv2025

Macrophages drive inguinal fat pad and lymph node remodelling in response to peripheral inflammation.

Adaptive immune responses are intensely energy-dependent and rely on a local source of fuel-producing molecules which have been proposed to be derived from fat pads in which mammalian lymph nodes are embedded. However, the trigger for their release has not been identified. Here we demonstrate that cutaneous inflammation is directly correlated with rapid atrophy of perinodal fat pads and increase in embedded lymph node size. We further demonstrate that the fat pad atrophy is associated with influx of a CCR2-independent, lipid metabolising, macrophage population. Macrophage depletion ameliorates fat pad atrophy, and lymph node expansion, downstream of inflamed sites. Our data therefore identify peripheral inflammation as an antigen-independent trigger of downstream fat pad and lymph node remodelling and contributes to the release of essential nutrients to drive the energetic requirements of the adaptive immune response.

immunology↗

bioRxiv2025

Inflammatory chemokine receptors CCR1, CCR2, CCR3 and CCR5 are essential for an optimal T cell response to influenza.

Inflammatory chemokine receptors CCR1/2/3/5 (iCCRs) play an important role in the recruitment of immune cells involved in innate immune functions and orchestrating the adaptive immune response. Here we utilise an influenza A virus (IAV) challenge to investigate the combinatorial roles of the iCCRs in the anti-IAV immune response. We did not observe any gross differences in infection-driven pathology in the absence of iCCRs. Despite iCCR deletion resulting in decreased migration of monocytes, migratory macrophages and B cells to lungs during acute IAV infection, no differences in dendritic cell numbers were observed. Whilst the total number of T cells was similar in lungs of iCCR-deficient mice, the number of IAV-specific CD4 but not CD8 T cells in the lung was strongly reduced in the absence of iCCRs. Furthermore, fewer CD4, but not CD8, T cells produced IFN-{gamma}. This CD4 T cell phenotype persisted into the memory stage of infection, with fewer IAV-specific and IFN-{gamma}+ CD4 but not CD8 T cells at 29 days post infection. In conclusion, despite having no impact on dendritic cell migration between the lung and the draining lymph node, iCCR deletion is associated with an altered CD4 T cell response to IAV infection.

immunology↗

bioRxiv2024

Eosinophils promote monocyte to macrophage differentiation and anti-bacterial immunity

Chemokine receptors control cell migration within the body. Here we reveal a novel interaction between eosinophils and monocytes in the bone marrow, indirectly controlled by the atypical chemokine receptor ACKR2. We demonstrate that ACKR2 maintains eosinophil levels within the bone marrow by scavenging CCL11. In the absence of ACKR2, elevated CCL11 leads to increased egress of eosinophils from the bone marrow into the bloodstream. As a result, eosinophil and monocyte interactions are reduced within the bone marrow niche, leading to changes in monocyte gene expression. Monocytes from ACKR2-/- mice are recruited to the tissues but are fundamentally altered in their ability to differentiate into macrophages, in the lung, peritoneal cavity and cavity wall. Bacterial elimination is impaired in ACKR2-/- mice during peritoneal infection. ACKR2 is therefore a key regulator of eosinophil-driven monocyte education in the bone marrow, required for full monocyte differentiation and macrophage function within the tissues.

immunology↗

bioRxiv2021

Analysis of combinatorial chemokine receptor expression dynamics using multi-receptor reporter mice

Inflammatory chemokines and their receptors are central to the development of inflammatory/immune pathologies. The apparent complexity of this system, coupled with lack of appropriate in vivo models, has limited our understanding of how chemokines orchestrate inflammatory responses and has hampered attempts at targeting this system in inflammatory disease. Novel approaches are therefore needed to provide crucial biological, and therapeutic, insights into the chemokine-chemokine receptor family. Here, we report the generation of transgenic multi-chemokine receptor reporter mice in which spectrally-distinct fluorescent reporters mark expression of CCRs 1, 2, 3 and 5, key receptors for myeloid cell recruitment in inflammation. Analysis of these animals has allowed us to define, for the first time, individual and combinatorial receptor expression patterns on myeloid cells in resting and inflamed conditions. Our results demonstrate that chemokine receptor expression is highly specific, and more selective than previously anticipated.

immunology↗