Chromatin-binding deubiquitinase MYSM1 acts in haematopoietic progenitors to control dendritic cell development and to program dendritic cell responses to microbial stimulation

Immunology. 2024 Feb 5. doi: 10.1111/imm.13758. Online ahead of print.ABSTRACTDendritic cells (DCs) are the most significant antigen presenting cells of the immune system, critical for the activation of naïve T cells. The pathways controlling DC development, maturation, and effector function therefore require precise regulation to allow for an effective induction of adaptive immune response. MYSM1 is a chromatin binding deubiquitinase (DUB) and an activator of gene expression via its catalytic activity for monoubiquitinated histone H2A (H2A-K119ub), which is a highly abundant repressive epigenetic mark. MYSM1 is an important regulator of haematopoiesis in mouse and human, and a systemic constitutive loss of Mysm1 in mice results in a depletion of many haematopoietic progenitors, including DC precursors, with the downstream loss of most DC lineage cells. However, the roles of MYSM1 at the later checkpoints in DC development, maturation, activation, and effector function at present remain unknown. In the current work, using a range of novel mouse models (Mysm1fl CreERT2 , Mysm1fl CD11c-cre, Mysm1DN ), we further the understanding of MYSM1 functions in the DC lineage: assessing the requirement for MYSM1 in DC development independently of other complex developmental phenotypes, exploring its role at the later checkpoints in DC maintenance and activation in response to microbial stimulation, and testing the requirement for the DUB catalytic activity of MYSM1 in these processes. S...
Source: Immunology - Category: Allergy & Immunology Authors: Source Type: research