Research group John Andersson
Research focus & projects
The immune system is the body's defense against infectious organisms. Furthermore, the immune system contributes to the progression of most of today’s non-communicable diseases including cancer and cardiovascular diseases. We study CD4+FOXP3+ regulatory T (Treg) cells that suppress immune activation and modulate the outcome of both inflammatory diseases and cancer. Treg cells depend on the transcription factor FOXP3 and mutations in the FOXP3 gene leads to a fatal lymphoproliferative disorder known as immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX). Treg cells have been extensively studied, however, two aspects of Treg cell biology remain unresolved. First, the transcription factor FOXP3 is required for Treg cell function, but the regulation and function of FOXP3 isoforms remain almost entirely unknown. Second, Treg cells inhibit immune responses by suppressing dendritic cells (DCs), but the exact mechanisms that Treg cells utilize remain controversial. The ultimate objective of our research program is to find new possibilities to control immune responses in humans by targeting Treg cells.
How does alternative splicing of FOXP3 impact immunity?
The transcription factor FOXP3 is essential for Treg function. FOXP3 exists in several distinct isoforms; however, the regulation and functional consequences of FOXP3 isoform expression remain poorly understood. We have found that FOXP3 isoforms have different or even opposing functions, and that different diseases are characterized by distinct patterns of FOXP3 isoform expression. What factors induce alternative splicing of FOXP3 mRNA? What distinct functions do the different FOXP3 isoforms confer? How do FOXP3 isoforms confer their different functions? We are using a combination of genetic and biochemical approaches to answer these questions.
How do Treg cells suppress dendritic cells?
The exact mechanisms and cellular targets of Treg cell-mediated suppression remain controversial. In vitro studies suggest that Treg cells have the capacity to directly suppress a large number of cell types including T cells and DCs. Many recent studies aiming to elucidate how Treg cells function have focused on Treg cells ability to suppress DCs as it is clear that Treg cells interact with DC in vivo. In order to define the exact mechanisms of suppression we have generated conditional knockout mice and are now combining in vivo studies with transcriptional profiling of in vitro suppressed DCs.
|Andersson, John, PhD, group leader|
|Joly, Anne-Laure, PhD, post doc|
|Seitz, Christina, MSc, PhD student|
Wallerius M, Wallmann T, Bartish M, Östling J, Mezheyeuski A, Tobin NP, Nygren E, Pangigadde PN, Pellegrini P, Squadrito M, Pontén F, Hartman J, Bergh J, De Milito A, De Palma M, Östman A, Andersson J, Rolny C. Guidance Molecule SEMA3A Restricts Tumor Growth by Differentially Regulating the Proliferation of Tumor-Associated Macrophages. Cancer Research 76:3166, 2016.
Mailer RKW, Joly A-L, Liu S, Elias S, Tegner J, Andersson J. IL-1β promotes Th17 differentiation by inducing alternative splicing of FOXP3. Scientific Reports 5:14674, 2015.
Joly A-L, Liu S, Dahlberg C, Mailer R, Westerberg L, Andersson J. Foxp3 lacking exons 2 and 7 is unable to confer suppressive ability to regulatory T cells in vivo. Journal of Autoimmunity 63:23, 2015.
Gisterå A, Robertson AKL, Andersson J, Ketelhuth DFJ, Ovchinnikova O, Nilsson SK, Lundberg AM, Li MO, Flavell RA, Hansson GK. Transforming growth factor-β signaling in T cells promotes stabilization of atherosclerotic plaques through an interleukin-17-dependent pathway. Science Translational Medicine 5:196ra100, 2013.
Tran DQ, Andersson J, Hardwick D, Bebris L, Illei GG, Shevach EM. Selective expression of latency-associated peptide (LAP) and IL-1 receptor type I/II (CD121a/CD121b) on activated human FOXP3+ regulatory T cells allows for their purification from expansion cultures. Blood 113:5125, 2009.
Tran DQ, Andersson J, Wang R, Ramsey H, Unutmaz D, Shevach EM. GARP (LRRC32) is essential for the surface expression of latent TGF-β on platelets and activated FOXP3+ regulatory T cells. Proceedings of the National Academy of Sciences of the United States of America 106:13445, 2009.
Pesu M, Watford WT, Wei L, Xu LL, Fuss I, Strober W, Andersson J, Shevach EM, Quezado M, Bouladoux N, Roebroek A, Belkaid Y, Creemers J, O'Shea JJ. T-cell-expressed proprotein convertase furin is essential for maintenance of peripheral immune tolerance. Nature 455: 246, 2008.
Andersson J, Tran DQ, Pesu M, Davidson TS, Ramsey H, O'Shea JJ, Shevach EM. CD4+Foxp3+ regulatory T cells confer infectious tolerance in a TGF-β-dependent manner. Journal of Experimental Medicine 205:1975, 2008.
Past and present funding
We gratefully acknowledge the funding from:
Stiftelsen Olle Engkvist Byggmästare
European Commission 7th framework program
Åke Wiberg Foundation
Clas Groschinsky FoundationKonung Gustaf V:s 80-årsfond
Magn. Bergvalls Stiftelse
Stiftelsen Sigurd och Elsa Goljes Minne
Gun och Bertil Stohnes stiftelse
Open positions and thesis projects
We are always interested to get in touch with talented potential co-workers. If you are interested in doing research within our group, as a post doc, PhD student or degree project student, please contact John Andersson (email: firstname.lastname@example.org).