Centre National De La Recherche Scientifique

Institut National De La Sante Et De La Recherche Medicale

Institut Pasteur De Lille

Université De Lille

Centre National De La Recherche Scientifique-Cnrs

Mathias Chamaillard

Corentin Lasseaux

Lionel Poulin

Monocytopoiesis is a hematological process that supplies the periphery with monocytes and subsequently with macrophages and monocyte-derived dendritic cells. Typically, monocytes circulate in the bloodstream for a very short time before undergoing apoptosis, however, stimulatory signals can trigger monocyte survival by inhibiting the apoptotic pathway, and thus contribute to the maintenance of the inflammatory response. Accordingly, there is a need for methods and pharmaceutical compositions for modulating monocytopoiesis. Now, the inventors show that type I interferons signaling promote the differentiation of monocyte-derived phagocytes at the level of their progenitors. Importantly, IFN-alpha and -beta were found to efficiently generate the development of monocyte-derived antigen-presenting cells while having no impact on the precursor activity of conventional dendritic cells. Accordingly, modulators of type I interferon (e.g. neutralizing antibodies or type I IFN polypeptides) would be suitable for modulating monocytopoiesis in subjects in need thereof.

Methods and pharmaceutical compositions for modulating monocytopoiesis

The present invention relates to the treatment of microbiome dysregulations. Said dysregulations may subsequently contribute to the development of several chronic diseases. Thus characterization of new post-biotic compounds inducing beneficial changes on host-microbiota interactions may be highly desirable. The inventors showed that Nlrp6 diurnally coordinates cyclical adaptation of the gut microbiota diversity to epithelial plasticity in response to a treatment with a Csnk2 inhibitor. The invention therefore relates to an inhibitor of Csnk2, for use in the treatment of microbiome dysregulations notably associated with circadian clock disruption. Said inhibitor may be selected among chemically synthesized or natural selective Csnk2 inhibitors such as flavones.

Methods and pharmaceutical compositions for treating microbiome dysregulations associated with circadian clock disruption

Growing community of inventors

Lille, France

Mathias Chamaillard