The essential role of Th17/Treg cells in inflammation and tumorigenesis
Project information
Project duration
-
Project funder
Project coordinator
University of Oulu
Unit and faculty
Contact information
Project leader
- Associate Professor (Tenure Track)Zhi Jane Chen
Project description
In recent years, Th17 and Treg cells have been identified to play critical roles in inflammatory diseases and tumor. Our proposal is to utilize state-of-the-art systems biology approaches combined with mouse models of human diseases to characterize recently identified players. We will investigate their roles in Th17/iTreg cell differentiation and function at multiple levels and from mouse to human. The results of this project are expected to reveal the molecular mechanisms of how these new players influence lymphocyte function in vitro, and consequently contributes to pathogenesis of inflammation and inflammation associated tumor in vivo. Data generated from this study will facilitate ongoing efforts in targeting these pathways to treat human diseases.
Key publications
Mohammad I, Nousiainen K, Bhosale SD, Starskaia I, Moulder R, Rokka A, Cheng F, Mohanasundaram P, Eriksson JE, Goodlett DR, Lähdesmäki H, Chen Z. Quantitative proteomic characterization and comparison of T helper 17 and induced regulatory T cells. PLoS Biol. May 31;16(5):e2004194. doi: 10.1371/journal.pbio.2004194. eCollection 2018.
Mohammad I, Starskaia I, Nagy T, Guo J, Yatkin E, Väänänen K, Watford WT, Chen Z. Estrogen receptor alpha contributes to T cell-mediated autoimmune inflammation by promoting T cell activation and proliferation. Sci Signal. Apr 17;11(526). pii: eaap9415. doi: 10.1126/scisignal.aap9415. 201
Tripathi S*, Chen Z*, Larjo A*, Kanduri K, Nousiainen K, Äijo T, Ricaño-Ponce I, Hrdlickova B, Tuomela S, Laajala E, Salo V, Kumar V, Wijmenga C, Lähdesmäki H, Lahesmaa R. Genome-wide analysis of STAT3 mediated transcription during early human Th17 cell differentiation. Cell Reports May 30;19(9):1888-1901.2017.
Outi Lindgren, Gwenaëlle Le Menn, Jussi Tuusa, Zhi Jane Chen, Kaisa Tasanen, Nina Kokkonen. Absence of NC14A Domain of COLXVII/BP180 in Mice Results in IL-17‒Associated Skin Inflammation. J Invest Dermatol. 2022 Aug 17;S0022-202X(22)01777-8. doi: 10.1016/j.jid.2022.07.019.
Laurence A, Tato CM, Davidson TS, Kanno Y, Chen Z, Yao Z, Blank RB, Meylan F, Siegel R, Hennighausen L, Shevach EM, O'shea JJ. Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity. 2007 Mar;26(3):371-81.
Chen Z, Laurence A, Kanno Y, Pacher-Zavisin M, Zhu BM, Tato C, Yoshimura A, Hennighausen L, O'Shea JJ.: Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells. Proc Natl Acad Sci USA. 2006 May 23;103(21):8137-42.
Roncagalli R, Hauri S, Fiore F, Liang Y, Chen Z, Sansoni A, Kanduri K, Joly R, Malzac A, Lähdesmäki H, Lahesmaa R, Yamasaki S, Saito T, Malissen M, Aebersold R, Gstaiger M, Malissen B. Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR signaling hub. Nat Immunol. 15(4):384-92. doi: 10.1038/ni.2843. 2014.
Chen Z, Tato CM, Muul L, Laurence A, O'Shea JJ. Distinct regulation of interleukin-17 in human T helper lymphocytes. Arthritis Rheum. 2007 Sep;56(9):2936-46.
Chen Z, Laurence A, O'Shea JJ. Signal transduction pathways and transcriptional regulation in the control of Th17 differentiation. Semin Immunol. 2007 Dec;19(6):400-8.
Jiang JK, Ghoreschi K, Deflorian F, Chen Z, Perreira M, Pesu M, Smith J, Nguyen DT, Liu EH, Leister W, Costanzi S, O'Shea JJ, Thomas CJ. Examining the chirality, conformation and selective kinase inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550). J Med Chem. 2008 Dec 25;51(24):8012-8.