Molecular Innate Immunity

Neuroinflammatory disorders, such as multiple sclerosis (MS), are initiated by inflammatory mediators produced by adaptive immune cells, such as T- and B- cells. These mediators trigger an inflammatory cascade that ultimately leads to tissue damage, executed by innate myeloid cells called macrophages. In acute lesions, both adaptive and innate immune cells contribute to this process. However, in chronic neuroinflammation, CNS-resident and hematopoietic stem cell (HSC)-derived macrophages predominate.

The molecular signals that drive macrophage effector programs to sustain neuroinflammation and neuroaxonal damage—independently of the initially dysregulated adaptive immune response—remain largely unknown.

Inflammation recurrence and immune aging, associated to late stage of MS and other chronic inflammatory disorders, may reprogram long-lived HSCs and myeloid progenitors to develop into pathogenic, self-sustaining macrophages. Our research focuses on identifying the triggers and molecular mechanisms underlying innate immune memory and immune aging in macrophages and their progenitors, which contribute to persistent tissue inflammation.

Leveraging uniquely available clinical samples and pathogenic process-specific experimental models, we aim to unravel the complex networks of signaling pathways, transcription factors, metabolic processes, and epigenetic modifications that regulate gene expression in innate myeloid cells during inflammation and aging. We use state of the art single-cell proteomics, genomics and metabolomics alongside in vivo functional studies, to dissect the molecular mechanisms governing the innate immune response. Our goal is to identify novel therapeutic targets to promote neuroinflammation resolution and slow down MS progression.