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Our group focuses on five areas of the immunology and neuroimmunology of cardiovascular diseases during aging:
- Define atherosclerosis as a bona fide autoimmune disease
- examine tolerance dysfunction in atherosclerosis
- identify the impact of artery tertiary lymphoid organs (ATLOs) on atherosclerosis
- delineate neuroimmune cardiovascular interfaces (NICIs) and artery-brain circuits (ABCs)
- study the choroid plexus as a major gateway for circulatory immune cells to enter the brain.
LATEST NEWS FROM THE LAB
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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.
- Tolerance dysfunction in atherosclerosis
Tolerance dysfunction as a driver of atherosclerosis progression is poorly understood. Using single cell RNA sequencing coupled with T cell receptor or B cell receptor profiling, we aim to identify abnormal tolerance checkpoints as disease drivers.
T cell tolerance breakdown in atherosclerosis. The immune system harbors checkpoints to maintain tolerance in secondary lymphoid organs to avoid autoimmune injury of self. These checkpoints appear to be compromised in a tissue-specific manner in atherosclerosis. Taken from Wang et al. Nat Cardiovasc Res. 2023;2(3):290-306.
The impact of artery tertiary lymphoid organs (ATLOs) on atherosclerosis
ATLOs in aged hyperlipidemic mice. T cells (in red) are a major cellular constituent of ATLOs. Green, smooth muscle cells in aortic media and in plaque. Blue, DAPI stained nuclei.
- 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.
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- Master students from Human Biology Master Program at LMU
- PhD candidates IRTG1123 program
Neuroimmune cardiovascular interfaces control atherosclerosis
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TEAM
GROUP MEMBERS
Sarajo Mohanta, PhDPrincipal InvestigatorRgpgküeOüzgubagvim-ävfsmi
Andreas Habenicht, MD PhDPrincipal Investigator
Changjun Yin, PhDPrincipal InvestigatorHzguxkfusØluvim-ful_vfiuyziutmi
Livia Habenicht, MDGuest Clinical Scientist
Ting Sun, PhDPostdoctoral researcher
Xinyi DengPhD studentÆluјleMiuxvim ävf mi
Xinwen DouPhD studentƒluéidau-m:üfvimeävf mi
Mingyang HongPhD studentO;;luaјgJux-Züuxvimeävf mi
Yutao LiPhD studentØfbgü Vlvimsfulhvfiuyziuemi
Mohammad Rafiee MonjeziPhD studentOüz:gvvgmdsBgwlDiivimeävfsmi
Zhihua WangPhD student, guest scientistLzlzfg Uguxvim ful_vfiuyziu mi
Xu XuPhD studentÆf Æfvim-ful_vfiuyziu mi
Xi ZhangPhD student:Æ Lzguxvim-f:ul_vfiuy;ziue:mi
Yixin ZhangPhD studentØlƒluJ Lzgux:vim ful_vfiuy:ziusmiAlumniYuanfang Li, former PhD student
Shu Lu, former PhD Student
Zhe Ma, former PhD student
Chuankai Zhang, former PhD student
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- 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
More Publications- Wagner JUG, Tombor LS, Malacarne PF, Kettenhausen LM, Panthel J, Kujundzic H, Manickam N, Schmitz K, Cipca M, Stilz KA, Fischer A, Muhly-Reinholz M, Abplanalp WT, John D, Mohanta SK, Weber C, Habenicht AJR, Buchmann GK, Angendohr S, Amin E, Scherschel K, Klocker N, Kelm M, Schuttler D, Clauss S, Gunther S, Boettger T, Braun T, Bar C, Pham MD, Krishnan J, Hille S, Muller OJ, Bozoglu T, Kupatt C, Nardini E, Osmanagic-Myers S, Meyer C, Zeiher AM, Brandes RP, Luxan G and Dimmeler S. Aging impairs the neurovascular interface in the heart. Science 2023
- 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, Godinho-Silva C, Veiga-Fernandes H, Xu QJ, Chang RB, Habenicht AJR. Cardiovascular Brain Circuits. Circ Res 2023
- Mohanta SK, Yin C, Weber C, Habenicht AJR. Neuroimmune cardiovascular interfaces in atherosclerosis. Front Cell Dev Biol 2023
- Mohanta SK, Weber C, Yin C, Habenicht AJR. The dawn has come for new therapeutics to treat atherosclerosis: Targeting neuroimmune cardiovascular interfaces in artery brain circuits. Clin Transl Med 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
- Wang Z, Zhang X, Zhang C, Li Y, Lu S, Mohanta S, Weber C, Habenicht A and Yin C. Combined Single-Cell RNA and Single-Cell alpha/beta T Cell Receptor Sequencing of the Arterial Wall in Atherosclerosis. Methods Mol Biol. 2022
- Sun T, Li Y, Forstera B, Stanic K, Lu S, Steffens S, Yin C, Erturk A, Megens RTA, Weber C, Habenicht A and Mohanta SK. Tissue Clearing Approaches in Atherosclerosis. 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
- Varasteh Z, De Rose F, Mohanta S, Li Y, Zhang X, Miritsch B, Scafetta G, Yin C, Sager HB, Glasl S, Gorpas D, Habenicht AJR, Ntziachristos V, Weber WA, Bartolazzi A, Schwaiger M and D'Alessandria C. Imaging atherosclerotic plaques by targeting Galectin-3 and activated macrophages using ((89)Zr)-DFO- Galectin3-F(ab')(2) mAb. Theranostics. 2021
- 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
- Bianchini M, Duchene J, Santovito D, Schloss MJ, Evrard M, Winkels H, Aslani M, Mohanta SK, Horckmans M, Blanchet X, Lacy M, von Hundelshausen P, Atzler D, Habenicht A, Gerdes N, Pelisek J, Ng LG, Steffens S, Weber C and Megens RTA. PD-L1 expression on nonclassical monocytes reveals their origin and immunoregulatory function. Sci Immunol. 2019
- Hu D, Yin C, Luo S, Habenicht AJR and Mohanta SK. Vascular Smooth Muscle Cells Contribute to Atherosclerosis Immunity. Front Immunol. 2019
- Newland SA, Mohanta S, Clement M, Taleb S, Walker JA, Nus M, Sage AP, Yin C, Hu D, Kitt LL, Finigan AJ, Rodewald HR, Binder CJ, McKenzie ANJ, Habenicht AJ and Mallat Z. Type-2 innate lymphoid cells control the development of atherosclerosis in mice. Nature communications. 2017
- Yin C, Mohanta SK, Srikakulapu P, Weber C and Habenicht AJ. Artery Tertiary Lymphoid Organs: Powerhouses of Atherosclerosis Immunity. Front Immunol. 2016
- 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. Arteriosclerosis, thrombosis, and vascular biology. 2016;36:1174-85.
- 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;42:1100-15.
- Mohanta SK, Yin C, Peng L, Srikakulapu P, Bontha V, Hu D, Weih F, Weber C, Gerdes N and Habenicht AJ. Artery tertiary lymphoid organs contribute to innate and adaptive immune responses in advanced mouse atherosclerosis. Circ Res. 2014;114:1772-87.
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Sarajo Mohanta, PhDPrincipal Investigator
Andreas Habenicht, MD PhDPrincipal Investigator+49 (0)89/4400-54679
Changjun Yin, PhDPrincipal Investigator
Livia Habenicht, MDGuest Clinical Scientist
Ting Sun, PhDPostdoctoral researcher+49 (0)89/4400-54635
Xinyi DengPhD student
Xinwen DouPhD student
Mingyang HongPhD student
Yutao LiPhD student
Mohammad Rafiee MonjeziPhD student
Zhihua WangPhD student, guest scientist
Xu XuPhD student
Xi ZhangPhD student
Yixin ZhangPhD student
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