Lack of mTORC2 signalling in CD11c+ myeloid cells inhibits their migration and ameliorates experimental colitis

J Leukoc Biol. 2024 Apr 23:qiae084. doi: 10.1093/jleuko/qiae084. Online ahead of print.ABSTRACTThe Mammalian Target of Rapamycin (mTOR) pathway plays a key role in determining immune cells function through modulation of their metabolic status. By specific deletion of Rictor in CD11c+ myeloid cells (referred to here as CD11cRicΔ/Δ), this study investigated the role of mTOR complex 2 (mTORC2) signalling in dendritic cells (DCs) function in mice. We showed that upon DSS-induced colitis, lack of mTORC2 signalling CD11c+ cells diminishes colitis score, and abrogates dendritic cell (DC) migration to the mesenteric lymph nodes (MLN), thereby diminishing the infiltration of T helper (Th) 17 cells in the lamina propria (LP) and subsequent inflammation. These findings corroborate with abrogation of cytoskeleton organization and decreased activation of Rac1 and Cdc42 GTPases observed in CD11c+-mTORC2-deficient cells. Meta-analysis on colonic samples from ulcerative colitis (UC) patients revealed increased gene expression of pro-inflammatory cytokines which coincided with augmented expression of mTOR pathway, positive correlation between the DC marker ITGAX and IL-6, the expression of RICTOR, and CDC42. Together, this work proposes that targeting mTORC2 on DCs offers a key to hamper inflammatory responses and this way, ameliorates the progression and severity of intestinal inflammatory diseases.PMID:38652699 | DOI:10.1093/jleuko/qiae084

Source: Journal of Leukocyte Biology - April 23, 2024 Category: Hematology Authors: Aline Ignacio Marcella Cipelli Tatiane Takiishi Cristhiane Favero Aguiar Fernanda Fernandes Terra Bruno Ghirotto Eloisa Martins Silva Angela Castoldi Yuli Thamires Magalh ães Tiago Antonio Barbara Nunes Padovani Meire Ioshie Hiyane Vinicius Andrade-Olive Source Type: research