Lena ALEXOPOULOU – CIML

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About

Dr. Lena Alexopoulou received her PhD in Molecular Genetics from the University of Athens, Greece. During her postdoctoral training at Yale University in the laboratory of Prof. Richard Flavell, she made seminal contributions to defining how distinct TLRs detect microbial ligands and trigger protective immune responses. Most notably, she discovered that TLR3 senses viral double-stranded RNA (Nature, 2001), a landmark discovery that provided the first evidence of a mammalian TLR acting as a sentinel in viral infection that paved the way for research on immunity and autoimmunity. She also identified the roles of TLR1 in detecting bacterial lipoproteins (Nat Med, 2002) and TLR7 in recognizing single-stranded RNA viruses (PNAS, 2004).

In 2004, she established her research group at the CIML, where she focused on TLR-mediated inflammation and autoimmunity. Her team identified TLR5 as the receptor for bacterial flagellin (PNAS, 2006) and discovered the critical role of TLR8 and TLR9 on acting as negative regulators of TLR7, thereby protecting against autoimmune pathology (J Clin Invest, 2010; PNAS, 2014). This work revealed a finely tuned regulatory interplay among nucleic-acid-sensing TLRs and demonstrated how its imbalance contributes to TLR7-mediated autoimmune diseases such as systemic lupus erythematosus and Sjögren's syndrome (Front Immunol, 2021; 2022). Her group further discovered that TLR7 signaling links lupus with high-fat diet–induced metabolic abnormalities, highlighting TLR7 as a promising therapeutic target bridging autoimmunity and metabolism (Front Immunol, 2019).

After leading her group at CIML from 2004 to 2018, she continued her research in the Stem Cell and Macrophage Biology group led by Dr. Michael Sieweke, and since 2024 she has been a member of the Immune Tolerance and T Cell Differentiation group led by Dr. Magali Irla. Her current work integrates her expertise in TLR biology with broader studies of immune tolerance, aiming to uncover novel mechanisms driving autoimmunity and chronic inflammation, and ultimately translating these insights into therapeutic strategies.

Lena Alexopoulou has published 80 peer-reviewed articles, more than half of which have been cited over 100 times (ORCID: 000-0003-4619-697X).

Publications

Alexopoulou L, Irla M, Toll-like receptors (TLRs) in the trained immunity era. Elife 2025 Sep; 14(): .

Subramanian S, Busch CJ, Molawi K, Geirsdottir L, Maurizio J, Vargas Aguilar S, Belahbib H, Gimenez ..., Long-term culture-expanded alveolar macrophages restore their full epigenetic identity after transfer in vivo. Nat Immunol 2022 Mar; 23(3): 458-468.

Alexopoulou L, Nucleic acid-sensing toll-like receptors: Important players in Sjögren's syndrome. Front Immunol 2022; 13(): 980400.

Wang Y, Roussel-Queval A, Chasson L, Hanna Kazazian N, Marcadet L, Nezos A, Sieweke MH, Mavragani C,..., TLR7 Signaling Drives the Development of Sjögren's Syndrome. Front Immunol 2021; 12(): 676010.

Hanna Kazazian N, Wang Y, Roussel-Queval A, Marcadet L, Chasson L, Laprie C, Desnues B, Charaix J, I..., Lupus Autoimmunity and Metabolic Parameters Are Exacerbated Upon High Fat Diet-Induced Obesity Due to TLR7 Signaling. Front Immunol 2019; 10(): 2015.

Desnues B, Macedo AB, Ordoñez-Rueda D, Roussel-Queval A, Malissen B, Bruhns P, Malissen M, Alexopou..., The transcriptional repressor Gfi1 prevents lupus autoimmunity by restraining TLR7 signaling. Eur J Immunol 2016 Dec; 46(12): 2801-2811.

Desnues B, Macedo AB, Roussel-Queval A, Bonnardel J, Henri S, Demaria O, Alexopoulou L, TLR8 on dendritic cells and TLR9 on B cells restrain TLR7-mediated spontaneous autoimmunity in C57BL/6 mice. Proc Natl Acad Sci USA 2014 Jan; 111(4): 1497-502.

Young GR, Eksmond U, Salcedo R, Alexopoulou L, Stoye JP, Kassiotis G, Resurrection of endogenous retroviruses in antibody-deficient mice. Nature 2012 Nov; 491(7426): 774-8.

Alexopoulou L, Desnues B, Demaria O, [Toll-like receptor 8: the awkward TLR]. Med Sci (Paris) 2012 Jan; 28(1): 96-102.

Traub S, Demaria O, Chasson L, Serra F, Desnues B, Alexopoulou L, Sex bias in susceptibility to MCMV infection: implication of TLR9. PLoS One 2012;7(9):e45171.

Demaria O, Pagni PP, Traub S, de Gassart A, Branzk N, Murphy AJ, Valenzuela DM, Yancopoulos GD, Flav..., TLR8 deficiency leads to autoimmunity in mice. J Clin Invest 2010 Oct; 120(10): 3651-62.

Pagni PP, Traub S, Demaria O, Chasson L, Alexopoulou L, Contribution of TLR7 and TLR9 signaling to the susceptibility of MyD88-deficient mice to myocarditis. Autoimmunity 2010 Jun; 43(4): 275-87.

Leaflet V, Medjane S, Mondor I, Demaria O, Pagni PP, Galán JE, Flavell RA, Alexopoulou L, Involvement of Toll-like receptor 5 in the recognition of flagellated bacteria. Proc Natl Acad Sci USA 2006 Aug; 103(33): 12487-92.

Wang T, Town T, Alexopoulou L, Anderson JF, Fikrig E, Flavell RA, Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nat Med 2004 Dec; 10(12): 1366-73.

Lund JM, Alexopoulou L, Sato A, Karow M, Adams NC, Gale NW, Iwasaki A, Flavell RA, Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc Natl Acad Sci USA 2004 Apr; 101(15): 5598-603.

Alexopoulou L, Thomas V, Schnare M, Lobet Y, Anguita J, Schoen RT, Medzhitov R, Fikrig E, Flavell RA, Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice. Nat Med 2002 Aug; 8(8): 878-84.

Alexopoulou L, Holt AC, Medzhitov R, Flavell RA, Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 2001 Oct; 413(6857): 732-8.