Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy.

Myocarditis can develop into inflammatory cardiomyopathy through chronic stimulation of myosin heavy chain 6-specific T helper (T)1 and T17 cells. However, mechanisms governing the cardiotoxicity programming of heart-specific T cells have remained elusive. Using a mouse model of spontaneous autoimmune myocarditis, we show that progression of myocarditis to lethal heart disease depends on cardiac myosin-specific T17 cells imprinted in the intestine by a commensal species peptide mimic.

Myocarditis Elicits Dendritic Cell and Monocyte Infiltration in the Heart and Self-Antigen Presentation by Conventional Type 2 Dendritic Cells.

Autoimmune myocarditis often leads to dilated cardiomyopathy (DCM). Although T cell reactivity to cardiac self-antigen is common in the disease, it is unknown which antigen presenting cell (APC) triggers autoimmunity. Experimental autoimmune myocarditis (EAM) was induced by immunizing mice with α-myosin loaded bone marrow APCs cultured in GM-CSF.

Myocardial Infarction Primes Autoreactive T Cells through Activation of Dendritic Cells.

Peripheral tolerance is crucial for avoiding activation of self-reactive T cells to tissue-restricted antigens. Sterile tissue injury can break peripheral tolerance, but it is unclear how autoreactive T cells get activated in response to self. An example of a sterile injury is myocardial infarction (MI).

Alternative NF-κB signaling regulates mTEC differentiation from podoplanin-expressing precursors in the cortico-medullary junction.

The thymic epithelium forms specialized niches to enable thymocyte differentiation. While the common epithelial progenitor of medullary and cortical thymic epithelial cells (mTECs and cTECs) is well defined, early stages of mTEC lineage specification have remained elusive. Here, we utilized in vivo targeting of mTECs to resolve their differentiation pathways and to determine whether mTEC progenitors participate in thymocyte education.

Programmed death 1 protects from fatal circulatory failure during systemic virus infection of mice.

The inhibitory programmed death 1 (PD-1)-programmed death ligand 1 (PD-L1) pathway contributes to the functional down-regulation of T cell responses during persistent systemic and local virus infections. The blockade of PD-1-PD-L1-mediated inhibition is considered as a therapeutic approach to reinvigorate antiviral T cell responses. Yet previous studies reported that PD-L1-deficient mice develop fatal pathology during early systemic lymphocytic choriomeningitis virus (LCMV) infection, suggesting a host protective role of T cell down-regulation.

Tight control - decision-making during T cell-vascular endothelial cell interaction.

Vascular endothelial cells (ECs) form the inner layer of blood vessels and exert crucial functions during immune reactions including coagulation, inflammation, and regulation of innate immunity. Importantly, ECs can interact with T cells in an antigen-specific, i.e.

Cooperation of Th1 and Th17 cells determines transition from autoimmune myocarditis to dilated cardiomyopathy.

Myocarditis is a potentially lethal inflammatory heart disease of children and young adults that frequently leads to dilated cardiomyopathy (DCM). Since diagnostic procedures and efficient therapies are lacking, it is important to characterize the critical immune effector pathways underlying the initial cardiac inflammation and the transition from myocarditis to DCM. We describe here a T-cell receptor (TCR) transgenic mouse model with spontaneously developing autoimmune myocarditis that progresses to lethal DCM.