Immunoregulation and
Therapy of Autoimmune
Autoimmune Diseases and Cancer
The team includes 3 Inserm researchers, 1 university hospital researcher, 1 Inserm research engineer and welcomes Master’s students, PhD students and post-doctoral researchers.
We specialise in the study of CD4+Foxp3+ regulatory T cells (Tregs) in mice, humanised mice and humans, and of certain cytokines. We are working on the role of metabolism, co-stimulatory/co-inhibitory signals, IL-12 and TNF family cytokines and novel markers of Tregs in the control of autoimmune diseases and cancers.
A better understanding of the role of Tregs in these diseases allows us to propose innovative therapies.
Our research focus on 3 axes
- Treg
- Cytokines
- Co-stimulation
- Cancer
- Autoimmunity
- Biotherapy
1. Identity and diversity of Tregs to homeostasis
We are studying the transcriptomic identity of Tregs based on data from the laboratory and the literature.
This work has allowed us to characterise a consensus molecular signature of Tregs and to show the preferential expression of unexpected genes in these cells, such as the proenkephalin gene.
Beyond their common identity, Tregs are also diverse and exhibit different properties depending on their tissue localisation.
We are working on the mechanisms involved in the early colonisation of non-lymphoid tissues by Tregs, and on the biology of Tregs present in adipose tissue and their role in insulin resistance.
2. Function of Tregs in autoimmune diseases and cancers
We have developed mice with specific deficiencies of certain genes (encoding TNFR2, 4-1BB, ICOS, NF-kB or regulating cellular metabolism) in Tregs to better understand their role in autoimmune and inflammatory diseases and cancers.
This work allows us to decipher the mechanisms of Treg suppression in target tissues of autoimmune attacks and in tumors.
It also allows us to identify therapeutic targets for these diseases that can then be tested in humanised mice before their development in patients.
3. Biology of IL-27 and IL-35
IL-27 and IL-35 are two heterodimeric cytokines of the IL-12 family that play an important role in the regulation of T responses and the development of autoimmune diseases and cancers.
Our projects aim to better understand their expression profile in human immunopathology, and the mechanisms regulating their biogenesis and mode of action.
The opportunities
- Collection of conditional KO mice for the study of Tregs
- Bioinformatic study of the Tregs signature
- Physiopathology of inflammatory diseases and cancers
- Validation of new targets in inflammatory diseases
- Validation of new targets for cancer immunotherapy
Publications
Salomon BL. TNF and regulatory T cells: insights into the biology and therapeutic implications. Nat Rev Rheumatol. 2021. 17:487-504. PMID: 34226727.
Emilie R, Pouchy C, Khosravia M, Hilaire M, Grégoire S, Casrouge A, Kassem S, Sleurs D, Martin GH, Chanson N, Lombardi Y, Lalleb G, Wajant H, Auffray C, Lucas B, Marodon G, Grinberg-Bleyer Y and Salomon BL. Tissue-restricted control of established central nervous system autoimmunity by TNF receptor 2 expressing Treg cells. Proc Natl Acad Sci USA. 2021. 118:e2014043118. PMID: 33766913.
Lubrano di Ricco M, Ronin E, Collares D, Divoux J, Grégoire S, Wajant H, Gomes T, Grinberg-Bleyer Y, Baud V, Marodon G, Salomon BL. Tumor necrosis factor receptor family costimulation increases regulatory T-cell activation and function via NF-κB. Eur J Immunol. 2020. 50:972-985. doi: 10.1002/eji.201948393. PMID: 32012260.
Vallion R, Divoux J, Glauzy S, Ronin E, Lombardi Y, Lubrano di Ricco M, Grégoire S, Nemazanyy I, Durand A, Fradin D, Lucas B and Salomon BL. Regulatory T cell stability and migration are dependent on mTOR. J Immunol. 2020. 205:1799-1809. doi: 10.4049/jimmunol.1901480. PMID 32839235.
Cavé MC, Maillard S, Hildenbrand K, Mamelonet C, Feige MJ, Devergne O. Glycosaminoglycans bind human IL-27 and regulate its activity. Eur J Immunol. 2020. 50:1484-1499. doi: 10.1002/eji.202048558. PMID:32483835.
Larousserie F, Kebe D, Huynh T, Audebourg A, Tamburini J, Terris B, Devergne O. Evidence for IL-35 expression in diffuse large B-cell lymphoma and impact on the patient’s prognosis. Front Oncol. 2019. 9:563. doi:10.3389/fonc.2019.00563. PMID: 31316915.
Müller SI, Friedl A, Aschenbrenner I, Esser-von Bieren J, Zacharias M, Devergne O*, Feige MJ*. A folding switch regulates interleukin 27 biogenesis and secretion of its α-subunit as a cytokine. Proc Natl Acad Sci USA. 2019. 116:1585-1590. doi: 10.1073/pnas.1816698116. PMID:30651310. *Corresponding authors.
Zaragoza B, Chen X, Oppenheim JJ, Baeyens A, Gregoire S, Chader D, Gorochov G, Miyara M and Salomon BL. Suppressive activity of human Treg cells is maintained in the presence of TNF. Nat Med. 2016. 22:16-17.