LATEST NEWS FROM THE LAB

• Atherosclerosis autoimmunity

A fundamental unresolved issue in the pathogenesis of atherosclerosis is whether the advanced and clinically significant disease is associated with the generation of arterial wall-specific autoantigens recognized by autoimmune T cells or B cells. We have begun to isolate B-2 cells from diseased arteries, sequence their B cell receptors, clone and express the autoimmune antibodies and examine their role in atherosclerosis progression.

• Neuroimmune cardiovascular interfaces (NICIs).

As plaques lack innervation, the impact of neuronal control on atherosclerosis remains unknown. Because the peripheral nervous system uses the adventitia as their principle conduit to reach distant targets, we postulated that the peripheral nervous system may directly interact with diseased arteries. Surprisingly, wide-spread neuro-immune-cardiovascular interfaces (NICIs) arose in murine and human atherosclerosis: adventitia segments showed extensive axon networks which form an artery-brain-circuit. 

• The choroid plexus is a major gateway for immune cells of the vascular system to enter the brain

The choroid plexus is the principal gateway for blood-borne leukocytes to infiltrate the central nervous system in inflammatory and degenerative brain diseases. We identified a hitherto unrecognized choroid plexus pathology consisting of lipid and leukocytes. Demented Alzheimer Disease patients have higher lipid content in choroid plexus versus non-dementia cases.

• Neurovascular interfaces initiate the artery-brain-circuit (ABC)

Murine NICIs established the ABCs to regulate cardiovascular functions. Abdominal-adventitia nociceptive afferents forms afferent artery-brain projection through spinal cord termed ABC sensor, which is linked to an efferent arm termed ABC effector forming a brain-artery projection. The brain integrates these peripheral signals and sends compensatory efferent effector signals from the hypothalamus and medulla to arteries. 

• Master students from Human Biology Master Program at LMU

• Wang Z, Zhang X, Lu S, Zhang C, Ma Z, Su R, Li Y, Sun T, Li Y, Hong M, Deng X, Monjezi MR, Hristov M, Steffens S, Santovito D, Dornmair K, Ley K, Weber C, Mohanta SK, Habenicht AJR and Yin C. Pairing of single-cell RNA analysis and T cell antigen receptor profiling indicates breakdown of T cell tolerance checkpoints in atherosclerosis. Nat Cardiovasc Res 2023
• Mohanta SK, Sun T, Lu S, Wang Z, Zhang X, Yin C, Weber C, Habenicht AJR. The Impact of the Nervous System on Arteries and the Heart: The Neuroimmune Cardiovascular Circuit Hypothesis. Cells 2023
• Mohanta SK, Yin C, Weber C, Habenicht AJR. Neuroimmune cardiovascular interfaces in atherosclerosis. Front Cell Dev Biol 2023
• Mohanta SK, Yin C, Weber C, Godinho-Silva C, Veiga-Fernandes H, Xu QJ, Chang RB, Habenicht AJR. Cardiovascular Brain Circuits. Circ Res 2023
  
• Zhang X, Wang Z, Zhang C, Li Y, Lu S, Steffens S, Mohanta S, Weber C, Habenicht A and Yin C. Laser Capture Microdissection-Based mRNA Expression Microarrays and Single-Cell RNA Sequencing in Atherosclerosis Research. Methods Mol Biol 2022
• Mohanta SK, Peng L, Li Y, Lu S, Sun T, Carnevale L, Perrotta M, Ma Z, Forstera B, Stanic K, Zhang C, Zhang X, Szczepaniak P, Bianchini M, Saeed BR, Carnevale R, Hu D, Nosalski R, Pallante F, Beer M, Santovito D, Erturk A, Mettenleiter TC, Klupp BG, Megens RTA, Steffens S, Pelisek J, Eckstein HH, Kleemann R, Habenicht L, Mallat Z, Michel JB, Bernhagen J, Dichgans M, D'Agostino G, Guzik TJ, Olofsson PS, Yin C, Weber C, Lembo G, Carnevale D and Habenicht AJR. Neuroimmune cardiovascular interfaces control atherosclerosis. Nature 2022
• Yin C, Ackermann S, Ma Z, Mohanta SK, Zhang C, Li Y, Nietzsche S, Westermann M, Peng L, Hu D, Bontha SV, Srikakulapu P, Beer M, Megens RTA, Steffens S, Hildner M, Halder LD, Eckstein HH, Pelisek J, Herms J, Roeber S, Arzberger T, Borodovsky A, Habenicht L, Binder CJ, Weber C, Zipfel PF, Skerka C and Habenicht AJR. ApoE attenuates unresolvable inflammation by complex formation with activated C1q. Nature medicine. 2019
• Hu D, Yin C, Luo S, Habenicht AJR and Mohanta SK. Vascular Smooth Muscle Cells Contribute to Atherosclerosis Immunity. Front Immunol. 2019
• Srikakulapu P, Hu D, Yin C, Mohanta SK, Bontha SV, Peng L, Beer M, Weber C, McNamara CA, Grassia G, Maffia P, Manz RA and Habenicht AJ. Artery Tertiary Lymphoid Organs Control Multilayered Territorialized Atherosclerosis B-Cell Responses in Aged ApoE-/- Mice. ATVB 2016
• Hu D, Mohanta SK, Yin C, Peng L, Ma Z, Srikakulapu P, Grassia G, MacRitchie N, Dever G, Gordon P, Burton FL, Ialenti A, Sabir SR, McInnes IB, Brewer JM, Garside P, Weber C, Lehmann T, Teupser D, Habenicht L, Beer M, Grabner R, Maffia P, Weih F and Habenicht AJ. Artery Tertiary Lymphoid Organs Control Aorta Immunity and Protect against Atherosclerosis via Vascular Smooth Muscle Cell Lymphotoxin beta Receptors. Immunity 2015