ARHGAP45 controls naïve T‐ and B‐cell entry into lymph nodes and T‐cell progenitor thymus seeding

Abstract

T and B cells continually recirculate between blood and secondary lymphoid organs. To promote their trans‐endothelial migration (TEM), chemokine receptors control the activity of RHO family small GTPases in part via GTPase‐activating proteins (GAPs). T and B cells express several RHO‐GAPs, the function of most of which remains unknown. The ARHGAP45 GAP is predominantly expressed in hematopoietic cells. To define its in vivo function, we describe two mouse models where ARHGAP45 is ablated systemically or selectively in T cells. We combine their analysis with affinity purification coupled to mass spectrometry to determine the ARHGAP45 interactome in T cells and with time‐lapse and reflection interference contrast microscopy to assess the role of ARGHAP45 in T‐cell polarization and motility. We demonstrate that ARHGAP45 regulates naïve T‐cell deformability and motility. Under physiological conditions, ARHGAP45 controls the entry of naïve T and B cells into lymph nodes whereas under competitive repopulation it further regulates hematopoietic progenitor cell engraftment in the bone marrow, and T‐cell progenitor thymus seeding. Therefore, the ARGHAP45 GAP controls multiple key steps in the life of T and B cells.

Longitudinal associations of DNA methylation and sleep in children: a meta-analysis

“…This CpG in chromosome 19 is annotated to the ARHGAP45 gene, which has a circadian expression profile ( http://circadb.hogeneschlab.org/human , last accessed 2021/06/22). ARHGAP45 codes for a precursor of the histocompatibility antigen HA-1 and a GTPase activator for the Rho-type GTPases ( https://www.genecards.org/cgi-bin/carddisp.pl?gene=ARHGAP45&keywords=hmha1 , last accessed 2021/06/09) and has been linked to endothelial integrity and immune cell maturation [ 48 , 49 ]. In a previous study investigating the associations between DNA co-methylation modules and sleep in one of the cohorts included in this meta-analysis, namely Generation R, authors reported that a module containing a CpG located at ARHGAP27 was associated with actigraphy-assessed sleep duration [ 14 ].…”

Integration of Molecular Inflammatory Interactome Analyses Reveals Dynamics of Circulating Cytokines and Extracellular Vesicle Long Non-Coding RNAs and mRNAs in Heroin Addicts During Acute and Protracted Withdrawal

“…MSTRG.207040.2 targets ABCA7 and ARHGAP45 ( Figure 5 ). It has been reported that ABCA7 haplodeficiency disturbs microglial immune responses in the mouse brain, and that ARHGAP45 controls naïve T- and B- cell entry into lymph nodes and T cell progenitor thymus seeding ( 55 ). FcγR triggers inflammatory reactions in response to antigen-antibody complexes.…”

Integration of molecular inflammatory interactome analyses reveals dynamics of circulating cytokines and extracellular vesicle long non-coding RNAs and mRNAs in heroin addicts during acute and protracted withdrawal

“…5 ). It has been reported that ABCA7 haplodeficiency disturbs microglial immune responses in the mouse brain, and that ARHGAP45 controls naïve T- and B-cell entry into lymph nodes and T cell progenitor thymus seeding (50). FcγR triggers inflammatory reactions in response to antigen-antibody complexes.…”