Liver X receptors command the transcriptional and functional polarization of humnan macrophages - PhDData

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Liver X receptors command the transcriptional and functional polarization of humnan macrophages

The thesis was published by González de la Aleja Molina, Arturo, in April 2022, Universidad Complutense de Madrid.

Abstract:

Macrophages populate every tissue in the body, where are determinant to theirhomeostasis. To develop this crucial task, macrophages display a quasi-infinite spectrum ofphenotypes or “polarization states”, and these states are determined by tissue moleculesand substances present in their immediate surroundings. Thus, macrophages are extremelyplastic cells capable of sensing and adapting to their environment. During inflammation,macrophages exert pro-inflammatory and anti-inflammatory/resolving effector functions,which are crucial for tissue injury removal and return to homeostasis, and whose unbalancepromotes chronic inflammatory diseases.To simplify the study of macrophage polarization, we analyzed two extremepolarization states: proinflammatory and antiinflammatory macrophages. We differentiatedmonocytes in vitro from healthy blood donors to macrophages using GM-CSF and M-CSF,respectively. M-CSF primes macrophages for acquisition of an anti-inflammatory (IL10high)and immunosuppressive (protumoral) profile. GM-CSF is produced at sites of inflammationand primes macrophages for robust antigen-presenting, T cell-stimulatory (antitumoral) andpro-inflammatory activity (TNFhigh IL6high). Therefore, human proinflammatory macrophages(GM-MØ from now on) and human antiinflammatory macrophages (M-MØ from now on) resemble in vivo arthritis-related synovial macrophages and tumor associated macrophages, respectively…



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