Cutting Edge: Tissue Antigen Expression Levels Fine-Tune T Cell Differentiation Decisions In Vivo.

Immune homeostasis in peripheral tissues is, to a large degree, maintained by the differentiation and action of regulatory T cells (Treg) specific for tissue Ags. Using a novel mouse model, we have studied the differentiation of naive CD4 T cells into Foxp3 Treg in response to a cutaneous Ag (OVA). We found that expression of OVA resulted in fatal autoimmunity and in prevention of peripheral Treg generation.

The omentum harbors unique conditions in the peritoneal cavity to promote healing and regeneration for diaphragm muscle repair in mdx mice.

Although the primary cause of Duchenne muscular dystrophy (DMD) is a genetic mutation, the inflammatory response contributes directly to severity and exacerbation of the diaphragm muscle pathology. The omentum is a lymphoid organ with unique structural and immune functions serving as a sanctuary of hematopoietic and mesenchymal progenitors that coordinate immune responses in the peritoneal cavity. Upon activation, these progenitors expand and the organ produces large amounts of growth factors orchestrating tissue regeneration.

Omentum acts as a regulatory organ controlling skeletal muscle repair of mdx mice diaphragm.

Duchenne muscular dystrophy is a lethal X-linked muscle wasting disease due to mutations of the dystrophin gene leading to distinct susceptibility to degeneration and fibrosis among skeletal muscles. This study aims at verifying whether intense mdx diaphragm remodeling could be attributed to influences from the omentum, a lymphohematopoietic tissue rich in progenitor cells and trophic factors. Mdx omentum produces growth factors HGF and FGF and increased amounts of VEGF with pleiotropic actions upon muscular progenitors and myoblast differentiation.

Neoantigen Expression in Steady-State Langerhans Cells Induces CTL Tolerance.

The skin hosts a variety of dendritic cells (DCs), which act as professional APC to control cutaneous immunity. Langerhans cells (LCs) are the only DC subset in the healthy epidermis. However, due to the complexity of the skin DC network, their relative contribution to either immune activation or immune tolerance is still not entirely understood.

Persistent activation of omentum influences the pattern of muscular lesion in the mdx diaphragm.

The mdx (X chromosome-linked muscular dystrophy) mouse develops a multi-staged disorder characterized by muscle degeneration and reactive fibrosis. Skeletal muscles of mdx mice are not equally susceptible to degeneration. The aim of this study was to verify whether the intense remodeling of the mdx diaphragm could be attributed to influences from the peritoneal microenvironment and omentum, a lymphohematopoietic tissue rich in progenitor cells and trophic factors.

Characteristic pattern of skeletal muscle remodelling in different mouse strains.

Muscular injury associated with local inflammatory reaction frequently occurs in sports medicine, but the individual response and capacity of regeneration vary among subjects. Inflammatory cytokines are probably implicated in activation of repair mechanisms by specifically influencing tissue microenvironment. This work aimed to compare muscle tissue repair in different mouse lineages.

Nicotinic acetylcholine receptor activation reduces skeletal muscle inflammation of mdx mice.

Mdx mice develop an inflammatory myopathy characterized at different ages by myonecrosis with scattered inflammatory infiltrates followed by muscular regeneration and later persistent fibrosis. This work aimed to verify the putative anti-inflammatory role of nicotinic acetylcholine receptor (nAChR) in the mdx muscular lesion. Mitigation of myonecrosis and decreased TNFα production were accompanied by increased numbers of F4/80 macrophages expressing nAChRα7.

Pattern of metalloprotease activity and myofiber regeneration in skeletal muscles of mdx mice.

Matrix metalloproteases (MMPs) are key regulatory molecules in the formation, remodeling, and degradation of extracellular matrix components in both physiological and pathological processes. Skeletal muscles of mdx dystrophic mice show distinct patterns of inflammation and regeneration, suggesting that factors within the microenvironment influence the adaptive responses of muscles with predominantly slow-twitch or fast-twitch fibers. This study aimed to verify the pattern of MMP activity in gastrocnemius, soleus, and diaphragm muscles and correlate it with the regenerative capability at distinct stages of the mdx myopathy.