Team: Taras Kreslavskiy - Immunology and allergy
Taras obtained his PhD and 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 in 2018.
Our research interests lie in two overlapping areas – 1) cell proliferation in the immune system and self-renewal of tissue-resident leukocytes and 2) biology of innate-like T and B cells.
1. Transcriptional regulation of cell proliferation and self-renewal in the immune system. In tissues that undergo permanent regeneration such as epidermis or gut epithelium, self-renewal capacity is usually restricted to a dedicated population of stem cells. In the hematopoietic system self-renewal has a much broader distribution as many mature leukocyte subsets regain the ability to self-renew as a part of their differentiation program. This is exemplified by memory T and B lymphocytes, several innate-like lymphocyte subsets, as well as many tissue-resident macrophage populations. In contrast to hematopoietic stem cells, little is known about the molecular networks that underlie the reacquisition of self-renewal capacity of these cells. It is tempting to speculate that some of the molecular regulators of this process may be common across different classes of self-renewing leukocytes. We recently identified transcription factors Bhlhe40 and Bhlhe41 as crucial regulators of development and self-renewal in an innate-like B lymphocyte subset – B-1a cells (Kreslavsky et al, 2017). Our new results indicate that these factors play a much broader role in regulation of proliferation and self-renewal in the immune system. We are currently investigating their function in a number of other cell types of the innate and adaptive immune system.
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. We are actively engaged in this work on both the B cell (Kreslavsky et al, 2017) and the T cell (Kreslavsky et al, 2008: Kreslavsky et al 2009; Gleimer et al, 2012) sides and will continue to pursue this line of research.
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).
If you are interested in joining our team as postdoc, PhD or undergraduate student, please contact Taras Kreslavsky.
Selected publications of the PI.
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