Team: Taras Kreslavskiy
Our lab is interested in the mechanism of cell fate decisions made by innate-like and conventional lymphocytes.
Taras obtained his PhD from and did a short postdoc in the laboratory of Harald von Boehmer at the Dana-Farber Cancer Research Institute at Harvard University working on alpha-beta versus gamma-delta T cell lineage choice, transcriptional regulation of innate-like T cells and, as a member of the Immunological Genome Project (Immgen) consortium, transcriptional regulation of T cell development. He then undertook a postdoc in the laboratory of Meinrad Busslinger (IMP, Vienna) where he worked on transcriptional regulation of humoral immunity. He joined the Karolinska Institute as an assistant professor and started his lab at the Department of Medicine, Solna in 2018.
Taras Kreslavsky’s lab has two main research interests: 1) mechanisms of cell fate decisions in humoral immune responses underlying the formation of immunological memory and 2) biology of innate-like T and B cells.
1. Mechanisms of cell fate decisions in humoral immune responses underlying the formation of immunological memory.
Antigen-dependent B cell differentiation is an unusual developmental process, in which the two main outputs of the humoral immune response – antibody-secreting plasma cells and quiescent memory B cells – can be generated by two distinct pathways: either directly from early activated B cells, or after transition through a transcriptionally distinct germinal center (GC) B cell state.
The first pathway can generate antibody-secreting cells very rapidly, providing the first line of defense against pathogens. Participation in the GC reaction allows to increase the affinity of antibodies but takes longer time. Understanding these developmental paths is of crucial importance, as the quality of immunological memory can vary greatly after infection and vaccination, resulting in a different degree of protection during the subsequent microbial challenge. We are taking advantage of recently developed technologies to dissect cellular and molecular mechanisms that govern formation of these distinct waves of memory B cells and plasma cells and to probe their functional properties. Utilizing single-cell transcriptomics and fate mapping, we recently demonstrated that a large fraction of activated B cells very early after immunization loses access to antigen and undergoes ‘differentiation by default’ to non-germinal center-derived early memory B cells (Glaros et al, 2021) and identified transcription factor Bhlhe40 as a crucial negative regulator of the earliest stages of the GC response (Rauschmeier et al, in revision).
2. Biology of innate like lymphocytes. Lymphocytes of the adaptive immune system can be functionally split into two major groups. Conventional T and B cells are characterized by extremely broad antigen receptor repertoires and therefore can respond to a diverse variety of antigens, but their activation, expansion and differentiation into effector cells requires several days. In contrast, innate-like T and B cells, such as gamma-delta T cells, NKT cells and B-1 cells, exhibit focused antigen receptor repertoires and are maintained in a constantly pre-activated state. These cells are thought to provide the first line of defense against pathogens and/or play a role in tissue homeostasis and repair. While we have a fairly good understanding of the biological functions, antigen specificities, selection rules and transcriptional programs for most conventional subsets, this is not the case for the majority of innate-like populations. Many basic questions that for conventional lymphocytes were solved years or even decades ago remain unanswered for innate-like cells. For example, while we know what BCRs and alpha-beta TCRs can recognize, only a handful of gamma-delta TCR ligands is known so far and there is no general understanding of what can or cannot become a ligand for gamma-delta TCRs. Similarly, while the molecular regulation of conventional lymphocyte development is relatively well characterized, signaling pathways and transcription factor networks that guide differentiation of innate-like T and B cells are only starting to be untangled. Our lab tries to shed light on various aspects of the biology of both innate-like B cells (Kreslavskiy et al, 2017) and innate-like T cells (Kreslavskiy et al, 2008: Kreslavskiy et al 2009; Gleimer et al, 2012; Dunst et al 2020).
Annika obtained her PhD in the laboratory of Immo Prinz at Hanover Medical School where she worked on gamma-delta T cells and their role in autoimmunity and inflammation. This work resulted in a number of publications in peer-reviewed journals including Journal of Immunology, European Journal of Immunology, Nature Immunology, Journal of Experimental Medicine and Arthritis & Rheumatology. During her time in Hanover she also received several awards including a BioLegend PhD Prize and a Graduate Scholarship from the Novartis Foundation for Therapeutic Research. Her current research is supported by a fellowship from the German Research Foundation (DFG).
Vassilis has a Bachelor of Science in Molecular Biology & Genetics from the Democritus University of Thrace, Alexandroupolis, Greece and a Master of Medical Science in Biomedicine from Karolinska Institutet, Stockholm, Sweden. He joined the group in April 2018 and as a master’s student he worked on identifying ligands for orphan γδ T cell receptors. In November 2019, shortly after his graduation from the Master’s in Biomedicine at KI, he was selected for a KID-funded position to perform his PhD studies. Currently, he is interested on the cellular and molecular events that take place upon B cell activation.
Josefine completed her doctoral studies in the laboratory of Faustin Kamena and Kai Matuschewski at the Max Planck Institute for Infection Biology in Berlin, Germany, where she studied the host immune response to Plasmodium infection in a murine malaria model. For her postdoc, Josefine joined the laboratory of Sergei Nedospasov at the German Rheumatism Research Center (DRFZ) to study the role of TNF and its receptors in autoimmunity. Josefine joined our lab in the spring of 2018 and her research is supported by a postdoc fellowship awarded by the German Research Foundation (DFG).
Yuanyuan obtained her Master of Medicine in Pathology and Pathophysiology at Sichuan University in June 2019. In her previous research, she focused on migration of Neutrophils in mice, especially upon the dynamic regulation of integrin α4’s S-glutathionylation. Then She won the CSC-KI scholarship and became a doctoral student in Taras’ team. In her PhD project, she will study some basic immunological issues such as T cell tolerance in T cell development.
If you are interested in joining our team as postdoc, PhD or undergraduate student, please contact Taras Kreslavskiy.
Selected publications of the PI
Limited access to antigen drives the generation of early B cell memory while restraining the plasmablast response.
Glaros V. , R. Rauschmeier, A.V. Artemov, A. Reinhardt, S. Ols, A. Emmanouilidi, Gustafsson C., You Y., Mirabello, Å.K. Björklund, L. Perez, N.P. King, Månsson R., D. Angeletti, K. Loré, I. Adameyko, M. Busslinger, and T. Kreslavskiy.
Immunity, in press.
Recognition of synthetic polyanionic ligands underlies "spontaneous" reactivity of V gamma 1 gamma delta TCRs
Dunst J, Glaros V, Englmaier L, Sandoz PA, Onfelt B, Kisielow J and T Kreslavsky
J. Leukoc. Biol. 2020 107:1033-1044
Bhlhe40 and Bhlhe41 transcription factors regulate alveolar macrophage self-renewal and identity
Rauschmeier R, Gustafsson C, Reinhardt A, A-Gonzalez N, Tortola L, Cansever D, Subramanian S, Taneja R, Rossner MJ, Sieweke MH, Greter M, Månsson R, Busslinger M and T Kreslavsky
EMBO J. 2019 38:e101233
Control of B-1a cell development by instructive BCR signaling
Kreslavsky T, Wong JB, Fischer M, Skok JA, and M Busslinger
Curr Opin Immunol 2018 51:24-31.
The metabolite BH4 controls T cell proliferation in autoimmunity and cancer
Cronin SJF, Seehus C, Weidinger A, Talbot S, Reissig S, Seifert M, et al
Essential role for the transcription factor Bhlhe41 in regulating the development, self-renewal and BCR repertoire of B-1a cells.
Kreslavsky T, Vilagos B, Tagoh H, Poliakova DK, Schwickert TA, Wöhner M, et al
Nat. Immunol. 2017 04;18(4):442-455
Stable inhibitory activity of regulatory T cells requires the transcription factor Helios.
Kim HJ, Barnitz RA, Kreslavsky T, Brown FD, Moffett H, Lemieux ME, et al
Science 2015 Oct;350(6258):334-9
Cyclin C is a haploinsufficient tumour suppressor.
Li N, Fassl A, Chick J, Inuzuka H, Li X, Mansour MR, et al
Nat. Cell Biol. 2014 Nov;16(11):1080-91
Negative selection, not receptor editing, is a physiological response of autoreactive thymocytes.
Kreslavsky T, Kim HJ, Koralov SB, Ghitza D, Buch T, Cantor H, et al
J. Exp. Med. 2013 Sep;210(10):1911-8
The TAL1 complex targets the FBXW7 tumor suppressor by activating miR-223 in human T cell acute lymphoblastic leukemia.
Mansour MR, Sanda T, Lawton LN, Li X, Kreslavsky T, Novina CD, et al
J. Exp. Med. 2013 Jul;210(8):1545-57
The transcriptional landscape of αβ T cell differentiation.
Mingueneau M, Kreslavsky T, Gray D, Heng T, Cruse R, Ericson J, et al
Nat. Immunol. 2013 Jun;14(6):619-32
β-Selection-induced proliferation is required for αβ T cell differentiation.
Kreslavsky T, Gleimer M, Miyazaki M, Choi Y, Gagnon E, Murre C, et al
Immunity 2012 Nov;37(5):840-53
PLZF Controls the Expression of a Limited Number of Genes Essential for NKT Cell Function.
Gleimer M, von Boehmer H, Kreslavsky T
Front Immunol 2012 ;3():374
TCR-inducible PLZF transcription factor required for innate phenotype of a subset of gammadelta T cells with restricted TCR diversity.
Kreslavsky T, Savage AK, Hobbs R, Gounari F, Bronson R, Pereira P, et al
Proc. Natl. Acad. Sci. U.S.A. 2009 Jul;106(30):12453-8
T cell receptor-instructed alphabeta versus gammadelta lineage commitment revealed by single-cell analysis.
Kreslavsky T, Garbe AI, Krueger A, von Boehmer H
J. Exp. Med. 2008 May;205(5):1173-86
Lineage diversion of T cell receptor transgenic thymocytes revealed by lineage fate mapping.
Egawa T, Kreslavsky T, Littman DR, von Boehmer H
PLoS ONE 2008 Jan;3(1):e1512