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3 results on '"Bajenoff, M"'

1. A subset of Kupffer cells regulates metabolism through the expression of CD36

Author

Bleriot, C, Barreby, E, Dunsmore, G, Ballaire, R, Chakarov, S, Ficht, X, De Simone, G, Andreata, F, Fumagalli, V, Guo, W, Wan, G, Gessain, G, Khalilnezhad, A, Zhang, X, Ang, N, Chen, P, Morgantini, C, Azzimato, V, Kong, W, Liu, Z, Pai, R, Lum, J, Shihui, F, Low, I, Xu, C, Malleret, B, Kairi, M, Balachander, A, Cexus, O, Larbi, A, Lee, B, Newell, E, Ng, L, Phoo, W, Sobota, R, Sharma, A, Howland, S, Chen, J, Bajenoff, M, Yvan-Charvet, L, Venteclef, N, Iannacone, M, Aouadi, M, Ginhoux, F, Bleriot C., Barreby E., Dunsmore G., Ballaire R., Chakarov S., Ficht X., De Simone G., Andreata F., Fumagalli V., Guo W., Wan G., Gessain G., Khalilnezhad A., Zhang X. M., Ang N., Chen P., Morgantini C., Azzimato V., Kong W. T., Liu Z., Pai R., Lum J., Shihui F., Low I., Xu C., Malleret B., Kairi M. F. M., Balachander A., Cexus O., Larbi A., Lee B., Newell E. W., Ng L. G., Phoo W. W., Sobota R. M., Sharma A., Howland S. W., Chen J., Bajenoff M., Yvan-Charvet L., Venteclef N., Iannacone M., Aouadi M., Ginhoux F., Bleriot, C, Barreby, E, Dunsmore, G, Ballaire, R, Chakarov, S, Ficht, X, De Simone, G, Andreata, F, Fumagalli, V, Guo, W, Wan, G, Gessain, G, Khalilnezhad, A, Zhang, X, Ang, N, Chen, P, Morgantini, C, Azzimato, V, Kong, W, Liu, Z, Pai, R, Lum, J, Shihui, F, Low, I, Xu, C, Malleret, B, Kairi, M, Balachander, A, Cexus, O, Larbi, A, Lee, B, Newell, E, Ng, L, Phoo, W, Sobota, R, Sharma, A, Howland, S, Chen, J, Bajenoff, M, Yvan-Charvet, L, Venteclef, N, Iannacone, M, Aouadi, M, Ginhoux, F, Bleriot C., Barreby E., Dunsmore G., Ballaire R., Chakarov S., Ficht X., De Simone G., Andreata F., Fumagalli V., Guo W., Wan G., Gessain G., Khalilnezhad A., Zhang X. M., Ang N., Chen P., Morgantini C., Azzimato V., Kong W. T., Liu Z., Pai R., Lum J., Shihui F., Low I., Xu C., Malleret B., Kairi M. F. M., Balachander A., Cexus O., Larbi A., Lee B., Newell E. W., Ng L. G., Phoo W. W., Sobota R. M., Sharma A., Howland S. W., Chen J., Bajenoff M., Yvan-Charvet L., Venteclef N., Iannacone M., Aouadi M., and Ginhoux F.

Abstract

Tissue macrophages are immune cells whose phenotypes and functions are dictated by origin and niches. However, tissues are complex environments, and macrophage heterogeneity within the same organ has been overlooked so far. Here, we used high-dimensional approaches to characterize macrophage populations in the murine liver. We identified two distinct populations among embryonically derived Kupffer cells (KCs) sharing a core signature while differentially expressing numerous genes and proteins: a major CD206loESAM– population (KC1) and a minor CD206hiESAM+ population (KC2). KC2 expressed genes involved in metabolic processes, including fatty acid metabolism both in steady-state and in diet-induced obesity and hepatic steatosis. Functional characterization by depletion of KC2 or targeted silencing of the fatty acid transporter Cd36 highlighted a crucial contribution of KC2 in the liver oxidative stress associated with obesity. In summary, our study reveals that KCs are more heterogeneous than anticipated, notably describing a subpopulation wired with metabolic functions.

Published
2021

2. Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming

Author

De Simone, G, Andreata, F, Bleriot, C, Fumagalli, V, Laura, C, Garcia-Manteiga, J, Di Lucia, P, Gilotto, S, Ficht, X, De Ponti, F, Bono, E, Giustini, L, Ambrosi, G, Mainetti, M, Zordan, P, Benechet, A, Rava, M, Chakarov, S, Moalli, F, Bajenoff, M, Guidotti, L, Ginhoux, F, Iannacone, M, De Simone G., Andreata F., Bleriot C., Fumagalli V., Laura C., Garcia-Manteiga J. M., Di Lucia P., Gilotto S., Ficht X., De Ponti F. F., Bono E. B., Giustini L., Ambrosi G., Mainetti M., Zordan P., Benechet A. P., Rava M., Chakarov S., Moalli F., Bajenoff M., Guidotti L. G., Ginhoux F., Iannacone M., De Simone, G, Andreata, F, Bleriot, C, Fumagalli, V, Laura, C, Garcia-Manteiga, J, Di Lucia, P, Gilotto, S, Ficht, X, De Ponti, F, Bono, E, Giustini, L, Ambrosi, G, Mainetti, M, Zordan, P, Benechet, A, Rava, M, Chakarov, S, Moalli, F, Bajenoff, M, Guidotti, L, Ginhoux, F, Iannacone, M, De Simone G., Andreata F., Bleriot C., Fumagalli V., Laura C., Garcia-Manteiga J. M., Di Lucia P., Gilotto S., Ficht X., De Ponti F. F., Bono E. B., Giustini L., Ambrosi G., Mainetti M., Zordan P., Benechet A. P., Rava M., Chakarov S., Moalli F., Bajenoff M., Guidotti L. G., Ginhoux F., and Iannacone M.

Abstract

Kupffer cells (KCs) are highly abundant, intravascular, liver-resident macrophages known for their scavenger and phagocytic functions. KCs can also present antigens to CD8+ T cells and promote either tolerance or effector differentiation, but the mechanisms underlying these discrepant outcomes are poorly understood. Here, we used a mouse model of hepatitis B virus (HBV) infection, in which HBV-specific naive CD8+ T cells recognizing hepatocellular antigens are driven into a state of immune dysfunction, to identify a subset of KCs (referred to as KC2) that cross-presents hepatocellular antigens upon interleukin-2 (IL-2) administration, thus improving the antiviral function of T cells. Removing MHC-I from all KCs, including KC2, or selectively depleting KC2 impaired the capacity of IL-2 to revert the T cell dysfunction induced by intrahepatic priming. In summary, by sensing IL-2 and cross-presenting hepatocellular antigens, KC2 overcome the tolerogenic potential of the hepatic microenvironment, suggesting new strategies for boosting hepatic T cell immunity.

Published
2021

3. Multicolor fate mapping of Langerhans cell homeostasis

Author

Ghigo, C, Mondor, I, Jorquera, A, Nowak, J, Wienert, S, Zahner, Sonja, Clausen, Björn, Luche, H, Malissen, B, Klauschen, F, Bajenoff, M, Ghigo, C, Mondor, I, Jorquera, A, Nowak, J, Wienert, S, Zahner, Sonja, Clausen, Björn, Luche, H, Malissen, B, Klauschen, F, and Bajenoff, M

Abstract

Langerhans cells (LCs) constitute a network of immune sentinels in the skin epidermis that is seeded during embryogenesis. Whereas the development of LCs has been extensively studied, much less is known about the homeostatic renewal of adult LCs in "nonmanipulated" animals. Here, we present a new multicolor fluorescent fate mapping system and quantification approach to investigate adult LC homeostasis. This novel approach enables us to propose and provide evidence for a model in which the adult epidermal LC network is not formed by mature coequal LCs endowed with proliferative capabilities, but rather constituted by adjacent proliferative units composed of "dividing" LCs and their terminally differentiated daughter cells. Altogether, our results demonstrate the general utility of our novel fate-mapping system to follow cell population dynamics in vivo and to establish an alternative model for LC homeostasis.

Published
2013

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