Mikael Karlsson Group
B Cells and Autoinflammation
SLE is a complex autoimmune disease currently without cure and the current goal with the treatment is to minimize organ damage and flares of disease as well as comorbidities such as atherosclerosis. A major problem though, is that when the patients are diagnosed at the clinic there is already irreversible organ damage. Still, autoantibodies
occur years before disease onset and thus finding B cell directed treatments and novel clinical markers could stop the disease at an early stage. In our group we focus research on systemic immunological mechanisms originatingin the spleen. One rationale for this is that the spleen contains our largest pool of immune cells as well as specific subtypes and has evolved to sense and balance systemic immunity. Even though the focus is inflammatory mechanisms in SLE the findings from my group will be central for many inflammatory diseases and conditions. An example of this is that we have found that macrophage polarization driven by specific pattern recognition receptors can be targeted for immunotherapy for cancer using an antibody. We are currently moving forward to test this novel treatment and are generating anti-human antibodies that could be used in the clinic.
The picture summarizes the focus of our research. The nature of the antigen (Ag): self vs non-self will directly or indirectly affect B cell activation, including T cell dependency. The B cell will interact with different immune cells, including APCs and various innate lymphocytes that regulate access to antigen and provide soluble factors. Also Pattern Recognition Receptors (PPRs) such as scavenger receptors will influence the outcome of B cell activation and behavior.
Current projects and directions of our research
Mikael Karlsson graduated from Uppsala University 1997 and received his Ph.D. in 2000 from the same University where he studied under Prof. Birgitta Heyman. In 2005 he completed his postdoctoral research at the Rockefeller University in New York in the lab of prof. Jeffrey Ravetch. After this he joined the faculty at Dept. of Medicine at Karolinska Institutet, Stockholm receiving an Assistant prof. position appointed by the Swedish Research Council. In 2009 he became Associate professor and in 2010 he received a senior research position appointed by the Swedish Research Council. Since 2016 he is a Professor of Immunology at the department of Microbiology, Tumor and Cell biology. Dr Karlsson is an elected member of the Henry Kunkel Society of Immunology as well as a co-chair of the Swedish Society for Immunology and head of the KI inflammation and immunology network (KiiM).
Work: +46 8 524 86175
Fax: + 46 8 524 87150
MTC, Box 280,
Nobels väg 16
S-171 77 Stockholm,
|Vanessa Boura||PhD student, Graduate Student|
|CHENFEI HE||Graduate Student|
|Neel Nabar||Graduate Student|
|Silke Sohn||PhD student, Graduate Student|
Pia Dosenovic, Rockefeller University, USA, laboratory of Prof. Michel Nussenzweig.
Pia Larssen (supervisor, Susanne Gabrielsson) Pia.Larseen@ki.se
Monica Centa (supervisor, Stephen Malin) email@example.com
Melanie Pieber (supervisor, Robert Harris) firstname.lastname@example.org
Martina Soldemo, PhD-student (supervisor Gunilla Karlsson-Hedestam) Martina.Soldemo@ki.se
Anna Zoltowska (supervisor Gunnar Nilsson) Anna.Zoltowska@ki.se
Stephanie Hiltbrunner (supervisor Susanne Gabrielsson) Stephanie.Hiltbrunner@ki.se
Erik Holmgren (Lab photographer ) Erik.Holmgren@ki.se
Malin Winerdal (Lab visual artist) Malin.Winerdal@ki.se
Anna-Maria Georgoudaki, PhD: Dissertation 2015, Karolinska Institutet. Thesis Exploring Immunotherapeutic Targets in the Tumor Microenvironment (opponent: Prof. Siamon Gordon, Oxford University, UK). Anna-Maria left the lab for a postdoc at Rockefeller University, New York, USA.
Eva Hellqvist, Postdoc: Left the lab in 2015 for a second postdoc at department of Medicine, Huddinge, Karolinska Institutet.
Mattias Forsell, Postdoc: Left the lab in 2015 for a position as Assistant Professor at Umeå University.
Kajsa Prokopec, Postdoc: Did a joint postdoc with Harvard Med. School the lab of Prof. Michael Carroll. Kajsa left the lab in 2014 to do a second postdoc at the department of Medicine, Solna, Karolinska Institutet.
Yunying Chen, Postdoc/Assistant Professor: Left the lab in 2014. Yunying studied innate B cell activation in Allergy and Autoimmunity and left to pursue a continued science career in the biotech industry.
Emilie Grasset, PhD: Dissertation 2013, Karolinska Institutet. Thesis: Regulation of B cell Responses to Modified Self (opponent: Prof. John Kearney, University of Alabama, USA). Emilie left the lab for Postdoc at Mount Sinai School of medicine, New York, USA, supported by the Swedish Research Council.
Evelina Lindmark, PhD (co-supervisor): Dissertation 2013, Karolinska Institutet. Thesis: Studies on peripheral tolerance in AIRE deficient mice (opponent Dr Eric Meffre, Yale Univ, USA). Evelina continued as postdoc at dept. of Medicine, Karolinska Institutet.
Sara Lind, PhD: Dissertation 2010, Karolinska Institutet. Thesis: Innate Mechanisms Regulating B cell Activation in Inflammatory Diseases (opponent: Prof. Ann Marshak-Rothstein, Boston, USA). Sara left the lab for postoc at MBB, Karolinska Institutet.
Fredrik Wermeling, PhD: Dissertation 2010, Karolinska Institutet. Thesis: Innate Mechanisms regulating peripheral B cell tolerance (opponent: Prof. Keith Elkon, Washington, USA). Fredrik received a Wenner Gren fellow postdoc fellowship and left the lab for posdoc at the Rockefeller University, New York.
Emma Lindh, PhD: (co-supervisor) Dissertation 2009, Karolinska Institutet. Thesis: The autoimmune regulator; studies of immunological tolerance in mouse and man (opponent: Prof. Susanna Cardell, Gothenburg, Sweden). Emma left the lab for employment by the ITH biotech company as senior scientist.
Nina Mattsson, MSc: Left the lab in 2005 to work as a clinical research associate (CRA) for monitoring clinical trials.
University of Toronto, Toronto, Canada: Prof. Tak Mak
Rockefeller University, New York, USA: Prof. Jeffrey Ravetch
NIH, Bethesda, USA: Prof. Susan Pierce
Harvard Medical School, Boston, USA: Prof. Michael Carroll and Prof. Michael Brenner
University of Toronto, Toronto, Canada: Assoc. Prof. Tracy McGaha
University of St Antonio, Texas, USA: Assoc. Prof. Elisabet Leadbetter
University of Erlangen-Nurnberg, Germany: Prof. Falk Nimmerjahn and Prof. Diana Dudziak
Gothenburg University, Sweden: Dr Åsa Tivesten
Karolinska Institutet, Sweden: Prof. Göran Hansson, Dr Elisabet Svenungson, Prof. Gunilla Karlsson Hedestam, Prof. Robert Harris, Prof. Vivianne Malmström; Associate Professors, Lisa Westerberg, Susanne Gabrielsson, Benedict Chambers, Charlotte Rolny, Rikard Sandberg, Stephen Malin and Jonas Fuxe.
Uppsala University, Sweden: Dr Johan Botling
Umeå University, Sweden: Dr Malin Sund
Altered Marginal Zone B Cell Selection in the Absence of IκBNS.
J. Immunol. 2018 01;200(2):775-787
A Link Between a Common Mutation in CFTR and Impaired Innate and Adaptive Viral Defense.
J. Infect. Dis. 2017 Dec;216(10):1308-1317
Epithelial-mesenchymal transition in cancer metastasis through the lymphatic system.
Mol Oncol 2017 07;11(7):781-791
Neutrophils license iNKT cells to regulate self-reactive mouse B cell responses.
Nat. Immunol. 2016 Dec;17(12):1407-1414
Exosomal cancer immunotherapy is independent of MHC molecules on exosomes.
Oncotarget 2016 Jun;7(25):38707-38717
Selective Memory to Apoptotic Cell-Derived Self-Antigens with Implications for Systemic Lupus Erythematosus Development.
J. Immunol. 2016 10;197(7):2618-26
Cutting Edge: Marginal Zone Macrophages Regulate Antigen Transport by B Cells to the Follicle in the Spleen via CD21.
J. Immunol. 2016 09;197(6):2063-8
BAFF-secreting neutrophils drive plasma cell responses during emergency granulopoiesis.
J. Exp. Med. 2016 07;213(8):1537-53
Reprogramming Tumor-Associated Macrophages by Antibody Targeting Inhibits Cancer Progression and Metastasis.
Cell Rep 2016 05;15(9):2000-11
Sensitivity of dendritic cells to NK-mediated lysis depends on the inflammatory environment and is modulated by CD54/CD226-driven interactions.
J. Leukoc. Biol. 2016 10;100(4):781-789
Cognate interaction with iNKT cells expands IL-10-producing B regulatory cells.
Proc. Natl. Acad. Sci. U.S.A. 2015 Oct;112(40):12474-9
Deletion of WASp and N-WASp in B cells cripples the germinal center response and results in production of IgM autoantibodies.
J. Autoimmun. 2015 Aug;62():81-92
Sterile inflammation in the spleen during atherosclerosis provides oxidation-specific epitopes that induce a protective B-cell response. Grasseta E, Duhlina A, Agardhb H, Ovchinnikovab O, Hägglöfa T, Forsella M, Paulsson-Berne, Hansson G, Ketelhuth D, Karlsson M. PNAS March 12 2015 doi: 10.1073/pnas.1421227112
IL-18 in inflammatory and autoimmune disease.
Cell. Mol. Life Sci. 2013 Dec;70(24):4795-808
Synergistic induction of adaptive antitumor immunity by codelivery of antigen with α-galactosylceramide on exosomes.
Cancer Res. 2013 Jul;73(13):3865-76
Independent expansion of epitope-specific plasma cell responses upon HIV-1 envelope glycoprotein immunization.
J. Immunol. 2013 Jul;191(1):44-51
AIRE expressing marginal zone dendritic cells balances adaptive immunity and T-follicular helper cell recruitment.
J. Autoimmun. 2013 May;42():62-70
BLyS-mediated modulation of naive B cell subsets impacts HIV Env-induced antibody responses.
J. Immunol. 2012 Jun;188(12):6018-26
Tolerance to apoptotic cells is regulated by indoleamine 2,3-dioxygenase.
Proc. Natl. Acad. Sci. U.S.A. 2012 Mar;109(10):3909-14
The inflammatory cytokine IL-18 induces self-reactive innate antibody responses regulated by natural killer T cells.
Proc. Natl. Acad. Sci. U.S.A. 2011 Dec;108(51):E1399-407
Marginal zone macrophages suppress innate and adaptive immunity to apoptotic cells in the spleen.
Blood 2011 May;117(20):5403-12
Invariant NKT cells limit activation of autoreactive CD1d-positive B cells.
J. Exp. Med. 2010 May;207(5):943-52
A regulatory role for macrophage class A scavenger receptors in TLR4-mediated LPS responses.
Eur. J. Immunol. 2010 May;40(5):1451-60
IL-18 skews the invariant NKT-cell population via autoreactive activation in atopic eczema.
Eur. J. Immunol. 2009 Aug;39(8):2293-301
AIRE regulates T-cell-independent B-cell responses through BAFF.
Proc. Natl. Acad. Sci. U.S.A. 2008 Nov;105(47):18466-71
Class A scavenger receptors regulate tolerance against apoptotic cells, and autoantibodies against these receptors are predictive of systemic lupus.
J. Exp. Med. 2007 Oct;204(10):2259-65