Mikael Karlsson Group

We research in B Cells and Autoinflammation.

Mechanism image
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. Photo: Mikael Karlsson

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.

Current projects and directions of our research

Current Projects Information Here

Contact

Work: +46 8 524 86175
Fax: + 46 8 524 87150

Address:
MTC, Box 280,
Nobels väg 16
Karolinska Institutet
S-171 77 Stockholm,
SWEDEN

Group Members

Associated People

Postdocs

  • Pia Dosenovic, Rockefeller University, USA, laboratory of Prof. Michel Nussenzweig.

Students

Other

Alumni

  • 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.

Collaborators

  • 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

Publications

All Mikael Karlsson Publications in PubMed

Gαi2 Signaling Regulates Inflammasome Priming and Cytokine Production by Biasing Macrophage Phenotype Determination.
Vural A, Nabar NR, Hwang IY, Sohn S, Park C, Karlsson MCI, et al
J. Immunol. 2019 03;202(5):1510-1520

Differential ACPA Binding to Nuclear Antigens Reveals a PAD-Independent Pathway and a Distinct Subset of Acetylation Cross-Reactive Autoantibodies in Rheumatoid Arthritis.
Lloyd KA, Wigerblad G, Sahlström P, Garimella MG, Chemin K, Steen J, et al
Front Immunol 2018 ;9():3033

Precocious expression of Blimp1 in B cells causes autoimmune disease with increased self-reactive plasma cells.
Bönelt P, Wöhner M, Minnich M, Tagoh H, Fischer M, Jaritz M, et al
EMBO J. 2019 01;38(2):

Innate and adaptive stimulation of murine diverse NKT cells result in distinct cellular responses.
Tripathi P, Sedimbi SK, Singh AK, Löfbom L, Issazadeh-Navikas S, Weiss S, et al
Eur. J. Immunol. 2019 03;49(3):443-453

Low-Density Lipoprotein-Reactive T Cells Regulate Plasma Cholesterol Levels and Development of Atherosclerosis in Humanized Hypercholesterolemic Mice.
Gisterå A, Klement ML, Polyzos KA, Mailer RKW, Duhlin A, Karlsson MCI, et al
Circulation 2018 11;138(22):2513-2526

Altered Marginal Zone B Cell Selection in the Absence of IκBNS.
Ádori M, Pedersen GK, Ádori C, Erikson E, Khoenkhoen S, Stark JM, et al
J. Immunol. 2018 01;200(2):775-787

A Link Between a Common Mutation in CFTR and Impaired Innate and Adaptive Viral Defense.
Svedin E, Utorova R, Hühn MH, Larsson PG, Stone VM, Garimella M, et al
J. Infect. Dis. 2017 12;216(10):1308-1317

The clinical importance of tumour-infiltrating macrophages and dendritic cells in periampullary adenocarcinoma differs by morphological subtype.
Lundgren S, Karnevi E, Elebro J, Nodin B, Karlsson MCI, Eberhard J, et al
J Transl Med 2017 07;15(1):152

Regulation of Subunit-Specific Germinal Center B Cell Responses to the HIV-1 Envelope Glycoproteins by Antibody-Mediated Feedback.
Forsell MNE, Kvastad L, Sedimbi SK, Andersson J, Karlsson MCI
Front Immunol 2017 ;8():738

The clinical importance of tumour-infiltrating macrophages and dendritic cells in periampullary adenocarcinoma differs by morphological subtype.
Lundgren S, Karnevi E, Elebro J, Nodin B, Karlsson MCI, Eberhard J, et al
J Transl Med 2017 07;15(1):152

Epithelial-mesenchymal transition in cancer metastasis through the lymphatic system.
Karlsson MC, Gonzalez SF, Welin J, Fuxe J
Mol Oncol 2017 07;11(7):781-791

Neutrophils license iNKT cells to regulate self-reactive mouse B cell responses.
Hägglöf T, Sedimbi SK, Yates JL, Parsa R, Salas BH, Harris RA, et al
Nat. Immunol. 2016 Dec;17(12):1407-1414

Exosomal cancer immunotherapy is independent of MHC molecules on exosomes.
Hiltbrunner S, Larssen P, Eldh M, Martinez-Bravo MJ, Wagner AK, Karlsson MC, et al
Oncotarget 2016 Jun;7(25):38707-38717

Selective Memory to Apoptotic Cell-Derived Self-Antigens with Implications for Systemic Lupus Erythematosus Development.
Duhlin A, Chen Y, Wermeling F, Sedimbi SK, Lindh E, Shinde R, et al
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.
Prokopec KE, Georgoudaki AM, Sohn S, Wermeling F, Grönlund H, Lindh E, et al
J. Immunol. 2016 09;197(6):2063-8

BAFF-secreting neutrophils drive plasma cell responses during emergency granulopoiesis.
Parsa R, Lund H, Georgoudaki AM, Zhang XM, Ortlieb Guerreiro-Cacais A, Grommisch D, et al
J. Exp. Med. 2016 07;213(8):1537-53

Deletion of Wiskott-Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells.
Baptista MA, Keszei M, Oliveira M, Sunahara KK, Andersson J, Dahlberg CI, et al
Nat Commun 2016 07;7():12175

Reprogramming Tumor-Associated Macrophages by Antibody Targeting Inhibits Cancer Progression and Metastasis.
Georgoudaki AM, Prokopec KE, Boura VF, Hellqvist E, Sohn S, Östling J, et al
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.
Smith LE, Olszewski MA, Georgoudaki AM, Wagner AK, Hägglöf T, Karlsson MC, et al
J. Leukoc. Biol. 2016 10;100(4):781-789

Apoptotic cell responses in the splenic marginal zone: a paradigm for immunologic reactions to apoptotic antigens with implications for autoimmunity.
McGaha TL, Karlsson MC
Immunol. Rev. 2016 Jan;269(1):26-43

Cognate interaction with iNKT cells expands IL-10-producing B regulatory cells.
Vomhof-DeKrey EE, Yates J, Hägglöf T, Lanthier P, Amiel E, Veerapen N, et al
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.
Dahlberg CI, Torres ML, Petersen SH, Baptista MA, Keszei M, Volpi S, et al
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.
Sedimbi SK, Hägglöf T, Karlsson MC
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.
Gehrmann U, Hiltbrunner S, Georgoudaki AM, Karlsson MC, Näslund TI, Gabrielsson S
Cancer Res. 2013 Jul;73(13):3865-76

Independent expansion of epitope-specific plasma cell responses upon HIV-1 envelope glycoprotein immunization.
Forsell MN, Soldemo M, Dosenovic P, Wyatt RT, Karlsson MC, Karlsson Hedestam GB
J. Immunol. 2013 Jul;191(1):44-51

AIRE expressing marginal zone dendritic cells balances adaptive immunity and T-follicular helper cell recruitment.
Lindmark E, Chen Y, Georgoudaki AM, Dudziak D, Lindh E, Adams WC, et al
J. Autoimmun. 2013 May;42():62-70

BLyS-mediated modulation of naive B cell subsets impacts HIV Env-induced antibody responses.
Dosenovic P, Soldemo M, Scholz JL, O'Dell S, Grasset EK, Pelletier N, et al
J. Immunol. 2012 Jun;188(12):6018-26

Tolerance to apoptotic cells is regulated by indoleamine 2,3-dioxygenase.
Ravishankar B, Liu H, Shinde R, Chandler P, Baban B, Tanaka M, et al
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.
Enoksson SL, Grasset EK, Hägglöf T, Mattsson N, Kaiser Y, Gabrielsson S, et al
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.
McGaha TL, Chen Y, Ravishankar B, van Rooijen N, Karlsson MC
Blood 2011 May;117(20):5403-12

Invariant NKT cells limit activation of autoreactive CD1d-positive B cells.
Wermeling F, Lind SM, Jordö ED, Cardell SL, Karlsson MC
J. Exp. Med. 2010 May;207(5):943-52

A regulatory role for macrophage class A scavenger receptors in TLR4-mediated LPS responses.
Chen Y, Wermeling F, Sundqvist J, Jonsson AB, Tryggvason K, Pikkarainen T, et al
Eur. J. Immunol. 2010 May;40(5):1451-60

IL-18 skews the invariant NKT-cell population via autoreactive activation in atopic eczema.
Lind SM, Kuylenstierna C, Moll M, D Jordö E, Winqvist O, Lundeberg L, et al
Eur. J. Immunol. 2009 Aug;39(8):2293-301

AIRE regulates T-cell-independent B-cell responses through BAFF.
Lindh E, Lind SM, Lindmark E, Hässler S, Perheentupa J, Peltonen L, et al
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.
Wermeling F, Chen Y, Pikkarainen T, Scheynius A, Winqvist O, Izui S, et al
J. Exp. Med. 2007 Oct;204(10):2259-65

Mikael Karlsson

Professor
C1 Department of Microbiology, Tumor and Cell Biology