DUCHENE MEGENS LAB | IPEK

DUCHENE MEGENS LAB - MOLECULAR INFLAMMATION

The main objective of our research is to uncover novel molecular mechanisms that control inflammation and immune responses.

Inflammation is a natural immune response triggered by harmful stimuli, such as infections or injuries. Its primary function is to protect the body against potential threats and to promote the healing of damaged tissue. Nevertheless, when inflammation is dysregulated and becomes chronic, it can contribute to the pathogenesis of many diseases. Inflammation is a complex mechanism involving the tightly orchestrated action of multiple inflammatory molecules.

Our research focuses on studying the chemokine system, a key player in regulating inflammation and immune responses.

Johan Duchene

Remco Megens
During the inflammatory response, chemokines govern the recruitment of circulating leukocytes and their migration to the inflamed sites. The effects of chemokines are mediated by G-protein coupled receptors (GPCRs), which are expressed in a wide range of immune cell types. Besides these "conventional" receptors (CCRs and CXCRs), chemokines also bind to atypical chemokine receptors (ACKRs), which control the availability of chemokines within tissues and thus influence immune cell behavior. The experimental work in our lab mainly focuses on the biology of ACKRs.
LATEST NEWS FROM THE LAB

Knocking Out Assumptions: Hidden Challenges in Transgenic Mouse Models

17 Oct 2024 | News | Publication

JLB 2024 ➤ IPEK scientists from the Duchene Lab have published critical findings on the limitations of genetic research using knockout mice.

IPEK at Chemokines Gordon Research Conference

7 Jun 2024 | News | Award | Conference

CONFERENCE HIGHLIGHT ➤ IPEK scientists from the Duchene Megens Lab participated in the Gordon Research Conference on Chemotactic Cytokines held in Portland, Maine, United States.

How antibodies get it wrong

CELL STEM CELL 2022 ➤ IPEK scientists alert to the wrong use of antibodies in scientific publications. In their recent work, they refute a specific study on localization of immune receptor ACKR1.
ACKR1 in immune response

ACKR1, also known as Duffy-antigen, binds 20+ inflammatory chemokines and was ascribed a unique expression profile in red blood cells, venular endothelial cells and Purkinje neurons. Individuals of African ancestry carry a genetic variant, rs2814778(G), in the gene encoding ACKR1. This variant results in the specific absence of ACKR1 expression on erythroid cells, causing a Duffy-negative phenotype. We generated a new mouse model that carries the mouse equivalent of the human rs2814778(G) polymorphism. We are currently investigating the function of erythroid-ACKR1 in the context of inflammatory diseases.

ACKR1 is expressed by CD31+ endothelial cells. Immunostaining showing the expression of ACKR1 in post-capillaries venules.

CXCL12-ACKR3 in cardiovascular disease

GWAS studies have linked the expression of CXCL12 to cardiovascular disease. However, there is still incomplete knowledge regarding the origin of CXCL12 and its role in attracting immune cells in the context of atherosclerosis, a chronic inflammatory disease of the arterial wall. Using advanced imaging technology, our research focuses on examining how immune cells migrate in human atherosclerotic plaques, with the aim of understanding their potential influence on atherosclerosis. Additionally, using transgenic mouse models, we explore the role of CXCL12 and its chemokine receptors, namely CXCR4 and ACKR3, in the context of atherosclerosis.

CD8+ T-cell invasion (arrow) in human plaque culture. The tissue was optically cleared and visualized using two-photon microscopy.

Western diet and hematopoeisis

Dietary factors have a substantial impact on overall health, and Western diet, even for a short period, not only disrupts arterial homeostasis but also affects hematopoiesis, the process responsible for immune cells production. Currently, using transgenic mouse models we investigate how short-term Western diet influences clonal hematopoiesis and the expansion of immune cells. Additionally, in collaboration with Dr. S. Frenz and Prof. C Klein, we are utilizing a newly developed human bone marrow organoid system to unravel the molecular mechanisms behind altered hematopoiesis induced by short-term Western diet.

Mouse bone marrow vasculature visualized using endoglin (stained in red) and laminin (stained in green). Sinusoids appear as red (laminin+ endoglin+) structures, and arteriole as green (lamininhi endoglin-) entities. Taken from Bianchini et al Thromb Haemost 2023
We are pleased to contribute to the education of students at different stages of their academic journey.

Master students from Human Biology Master Program at LMU
BioImaging - Practical course und Seminar (Course Catalogue Reference: 19254)
Heart, Lung and Metabolism - Practical course (Course Catalogue Reference: 19286)

Master students at LMU
Flow Cytometry & Optical Imaging – Seeing is Believing (Course Catalogue Reference: 7C0741)
Flow Cytometry in Clinical Practice (Course Catalogue Reference: 7C4072)

PhD candidates IRTG1123 program
Flow Cytometry
Microscopy Imaging
How to control your experiments?

Master students from Inflamex Master Program at University of Paris
Chemokine System
Kinin System
Johan Duchêne is a member of the LMU Open Science Center

"Changes in research are needed and I strongly believe that education is the way forward. As researchers, not only should we implement good research practices such as integrity, transparency, and reliability in our own labs but also train the next generation of scientists and provide them the tools to improve the quality of science"

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TEAM

GROUP MEMBERS

Johan Duchêne, PhD

Principal Investigator

+49 (0)89/4400-54757

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Remco T. A. Megens, PhD

Head of Microcopic Imaging

+49 (0)89/4400-54673

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Laura Parma, PhD

Postdoctoral researcher

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Savannah Fairley

PhD student

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Zoe Möller Ramon

PhD student

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Nikola Sobczak

PhD student

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Harini Balasubramanian

M.Sc. student

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Špela Barbič

M.Sc. student

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Khushboo Garg

M.Sc. student

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Tanishq Jain

M.Sc. student

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Niti Chowdhury

Research assistant (HiWi) student

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Olivera Veselinov

Research assistant (HiWi) student

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Yvonne Jansen

Technician

+49 (0)89/4400-52609

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Markus Haberbosch

Technician

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Alumni

Mariaelvy Bianchini, former PostDoc
Aindrila Biswas, former PostDoc
Bahram Khosravi, former PostDoc

Maria Aslani, former PhD student
Möller-Ramon Z, Aslani M, Sobczak N, Hristov M, Weber C, Rot A, Duchêne J. The 129 strain-derived passenger mutations in ACKR1-deficient mice alter the expression of PYHIN and Fc-gamma receptor genes. Journal of Leukocyte Biology 2024

Frenz-Wiessner S, Fairley SD, Buser M, Goek I, Salewskij K, Jonsson G, Illig D, Zu Putlitz B, Petersheim D, Li Y, Chen PH, Kalauz M, Conca R, Sterr M, Geuder J, Mizoguchi Y, Megens RTA, Linder MI, Kotlarz D, Rudelius M, Penninger JM, Marr C, Klein C. Generation of complex bone marrow organoids from human induced pluripotent stem cells. Nat Methods 2024

Bianchini M, Möller-Ramon Z, Weber C, Megens RTA, Duchene J. Short-term western diet causes rapid and lasting alterations of bone marrow physiology. Thromb Haemost 2023

Rot A, Gutjahr J.C, Biswas A, Aslani M, Hub E, Thiriot A, von Andrian U.H., Megens R.T.A, Weber C, Duchene J. Murine bone marrow macrophages and human monocytes do not express atypical chemokine receptor 1. Cell Stem Cell 2022

Barkaway A, Rolas L, Joulia R, Bodkin J, Lenn T, Owen-Woods C, Reglero-Real N, Stein M, Vázquez-Martínez L, Girbl T, Poston RN, Golding M, Saleeb RS, Thiriot A, von Andrian UH, Duchene J, Voisin MB, Bishop CL, Voehringer D, Roers A, Rot A, Lämmermann T, Nourshargh S. Age-related changes in the local milieu of inflamed tissues cause aberrant neutrophil trafficking and subsequent remote organ damage. Immunity. 2021

Gutjahr JC, Crawford KS, Jensen DR, Naik P, Peterson FC, Samson GPB, Legler DF, Duchene J, Veldkamp CT, Rot A, Volkman B. Dimeric form of CXCL12 binds to atypical chemokine receptor 1. Sci. Signal. 2021

Eckardt V, Miller MC, Blanchet X, Duan R, Leberzammer J, Duchene J, Soehnlein O, Megens RTA, Ludwig AK, Dregni A, Faussner A, Wichapong K, Ippel H, Dijkgraaf I, Kaltner H, Döring Y, Bidzhekov K, Hackeng TM, Weber C, Gabius HJ, von Hundelshausen P, Mayo KH. Chemokines and galectins form heterodimers to modulate inflammation. EMBO reports. 2020

Döring Y, Jansen Y, Cimen I, Aslani M, Gencer S, Peters LJF, Duchene J, Weber C, van der Vorst EPC. CXCL12 B-Cell–Specific CXCR4 Protects Against Atherosclerosis Development and Increases Plasma IgM Levels Circ Res. 2020

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, Megens RTA. PD-L1 expression on nonclassical monocytes reveals their origin and immunoregulatory function. Sci Immunol. 2019

Duchene J, Novitzky-Basso I, Thiriot A, Casanova-Acebes M, Bianchini M, Etheridge SL, Hub E, Nitz K, Artinger K, Eller K, Caamaño J, Rülicke T, Moss P, Megens RTA, von Andrian UH, Hidalgo A, Weber C, Rot A. Atypical chemokine receptor 1 on nucleated erythroid cells regulates hematopoiesis. Nat Immunol. 2017

Rousselle A, Qadri F, Leukel L, Yilmaz R, Fontaine JF, Sihn G, Bader M, Ahluwalia A, Duchene J. CXCL5 limits macrophage foam cell formation in atherosclerosis. J Clin Invest. 2013