Hermann-Kleiter Natascha, PD. Dr. rer. nat.

University / Clinic: Innsbruck Medical University
Institute: Department for Medical Genetics, Molecular and Clinical Pharmacology, Section for Translational Cell
 
Research Area: T cell biology

Email: natascha.kleiter@i-med.ac.at
Web: baierlab.com/

  Funded by: FWF

Research Topic:
The immune system protects our bodies against invasion by pathogens of viral, bacterial, fungal and parasitic origin and against growth of neoplastic cells. The intensity of the adaptive immune responses must be tightly regulated in terms of class and duration to allow the proper production of immune-regulatory cytokines or chemokines by T lymphocyte subsets and the differentiation of B cells. Particularly CD4+ `helper` T (Th) cells face the challenge of balancing stability and plasticity in their gene expression programs as they differentiate into their specialized as e.g. Th1, Th2, Th17, Tfh, or iTreg subsets.

Family members of the steroid/thyroid hormone family as e.g. the glucocorticoid receptor are well known for sensing external cues (such as hormones) in order to regulate the expression of specific genes thereby controlling immune reaction of the organism. The nuclear orphan receptors of the NRXY family are expressed in diverse adaptive and innate immune cells. We discovered a critical function of NRXY as a potent and selective repressor of pro-inflammatory cytokine transcription and autoimmune disorders. We study signaling cascades within T cells using a wide range of modern cell biological, cellular and mouse genetic approaches.
The focus of the projects is to understand how the NR signaling network is coupled to the T cell receptor (TCR) signaling cascade in order to enable selective interference during disease triggering immune responses as a long term perspective.


Project:
  Identify the role of NRXY family in the classical helper subset of CD4+ follicular Th (Tfh) cells
details ...

Selected publications:
 
  Pfeifhofer-Obermair C, Albrecht-Schgör K, Peer S, Nairz M, Siegmund K, Klepsch-Pedit V, Haschka D, Thuille N, Hermann-Kleiter N, Gruber T, Weiss G, Baier G
Role of PKCtheta in macrophage-mediated immune response to Salmonella typhimurium infection in mice.
Cell Commun Signal. 2016 Jul 28;14(1):14

  Siegmund K, Klepsch-Pedit V, Hermann-Kleiter N, Baier G
Proof of Principle for a T Lymphocyte Intrinsic Function of Coronin 1A.
J Biol Chem. 2016 Oct 14;291(42):22086-22092. Epub 2016 Aug 26.

  Klepsch-Pedit V, Hermann-Kleiter N, Baier G
Beyond CTLA-4 and PD-1: Orphan nuclear receptor NR2F6 as T cell signaling switch and emerging target in cancer immunotherapy.
Immunol Lett. 2016 Oct;178:31-6. doi: 10.1016/j.imlet.2016.03.007. Epub 2016 Mar 15.

  Hermann-Kleiter N, Klepsch-Pedit V, Wallner S, Siegmund K, Klepsch S, Tuzlak S, Villunger A, Kaminski S, Pfeifhofer-Obermair C, Gruber T, Wolf D, Baier G
The Nuclear Orphan Receptor NR2F6 Is a Central Checkpoint for Cancer Immune Surveillance.
Cell Rep. 2015 Sep 29;12(12):2072-85.

  Wachowicz K, Hermann-Kleiter N, Meisel M, Siegmund K, Thuille N, Baier G
Protein Kinase C θ regulates Th17/Th1 plasticity in mouse CD4+ T lymphocytes.
PLoS One. 2014 May 2;9(5).

  Hermann-Kleiter N, Baier G
Orphan nuclear receptor NR2F6 acts as an essential gatekeeper of Th17 CD4+ T cell effector functions.
Cell Commun Signal. 2014 Jun 12;12:38. doi: 10.1186/1478-811X-12-38.

  Gruber T, Hinterleitner R, Hermann-Kleiter N, Meisel M, Kleiter I, Wang C, Viola A, Pfeifhofer-Obermair C, Baier G
Cbl-b mediates TGFβ sensitivity by downregulating inhibitory SMAD7 in primary T cells.
J Mol Cell Biol. 2013 Jun 26

  Thuille N, Wachowicz K, Hermann-Kleiter N, Kaminski S, Fresser F, Lutz-Nicoladoni C, Leitges M, Thome M, Massoumi R, Baier G
PKCθ/β and CYLD are antagonistic partners in the NFκB and NFAT transactivation pathways in primary mouse CD3+ T lymphocytes.
PLoS One. 2013;8(1): Epub 2013 Jan 15.

  Meisel M, Hermann-Kleiter N, Hinterleitner R, Gruber T, Wachowicz K, Pfeifhofer-Obermair C, Fresser F, Leitges M, Soldani C, Viola A, Kaminski S, Baier G
The kinase PKCα selectively upregulates interleukin-17A during Th17 cell immune responses.
Immunity. 2013 Jan 24;38(1):41-52; Epub 2013 Jan 3.

  Bock FJ, Krumschnabel G, Manzl C, Peintner L, Tanzer MC, Hermann-Kleiter N, Baier G, Llacuna L, Yelamos J, Villunger A.
Loss of PIDD limits NF-κB activation and cytokine production but not cell survival or transformation after DNA damage.
Cell Death Differ. 2013 Apr;20(4):546-57

  Bock FJ, Krumschnabel G, Manzl C, Peintner L, Tanzer MC, Hermann-Kleiter N, Baier G, Llacuna L, Yelamos J, Villunger A.
Loss of PIDD limits NF-κB activation and cytokine production but not cell survival or transformation after DNA damage.
Cell Death Differ. 2012 Dec 14

  Hermann-Kleiter N, Meisel M, Fresser F, Thuille N, Müller M, Roth L, Katopodis A, Baier G
Nuclear orphan receptor NR2F6 directly antagonizes NFAT and RORγt binding to the Il17a promoter.
J Autoimmun. 2012 Dec;39(4):428-40.

  Kaminski S, Hermann-Kleiter N, Meisel M, Thuille N, Cronin S, Hara H, Fresser F, Penninger J, Baier G
Coronin 1A is an essential regulator of the TGFβ receptor/SMAD3 signaling pathway in Th17 CD4(+) T cells.
J Autoimmun. 2011 Nov;37(3):198-208. Epub 2011 Jun 22.

  Hermann-Kleiter N, Baier G
NFAT pulls the strings during CD4+ T helper cell effector functions
Blood;115(15):2989-97.

  Hermann-Kleiter N, Baier G
NFAT pulls the strings during CD4+ T helper cell effector functions.
Blood. 2010 Apr 15;115(15):2989-97.

  Gruber T, Hermann-Kleiter N, Pfeifhofer-Obermair C, Lutz-Nicoladoni C, Thuille N, Letschka T, Barsig J, Baudler M, Li J, Metzler B, Nüsslein-Hildesheim B, Wagner J, Leitges M, Baier G
PKC theta cooperates with PKC alpha in alloimmune responses of T cells in vivo.
Mol Immunol. 2009 Jun;46(10):2071-9. Epub 2009 Apr 7

  Evenou J, Wagner J, Zenke G, Brinkmann V, Wagner K, Kovarik J, Welzenbach K, Weitz-Schmidt G, Guntermann C, Towbin H, Cottens S, Kaminski S, Letschka T, Lutz-Nicoladoni C, Gruber T, Hermann-Kleiter N
The potent protein kinase C selective inhibitor AEB071 (Sotrastaurin)represents a new class of immunosuppressive agents affecting early T cell activation.
J Pharmacol Exp Ther. 2009 Jun 2. [Epub ahead of print]

  Gruber T, Hermann-Kleiter N, Hinterleitner R, Fresser F, Schneider R, Gastl G, Penninger J, Baier G
PKC-theta Modulates the Strength of T Cell Responses by Targeting Cbl-b for Ubiquitination and Degradation.
Science Signal. 2009 Jun 23;2(76):ra30

  Evenou J, Wagner J, Zenke G, Brinkmann V, Wagner K, Kovarik J, Welzenbach K, Weitz-Schmidt G, Guntermann C, Towbin H, Cottens S, Kaminski S, Letschka T, Lutz-Nicoladoni C, Gruber T, Hermann-Kleiter N
The potent protein kinase C-selective inhibitor AEB071 (sotrastaurin) represents a new class of immunosuppressive agents affecting early T-cell activation.
J Pharmacol Exp Ther. 2009 Sep;330(3):792-801.

  Gruber T, Hermann-Kleiter N, Pfeifhofer-Obermair C, Lutz-Nicoladoni C, Thuille N, Letschka T, Barsig J, Baudler M, Li J, Metzler B, Nüsslein-Hildesheim B, Wagner J, Leitges M, Baier G
PKC theta cooperates with PKC alpha in alloimmune responses of T cells in vivo.
Mol Immunol. 2009 Jun;46(10):2071-9.

  Hermann-Kleiter N, Gruber T, Lutz-Nicoladoni C, Thuille N, Fresser F, Labi V, Schiefermeier N, Warnecke M, Huber L, Villunger A, Eichele G, Kaminski S, Baier G.
The Nuclear Orphan Receptor NR2F6 Suppresses Lymphocyte Activation and T Helper 17-Dependent Autoimmunity
Immunity

  Hermann-Kleiter N, Gruber T, Lutz-Nicoladoni C, Thuille N, Fresser F, Labi V, Schiefermeier N, Warnecke M, Huber LA, Villunger A, Eichele G, Kaminski S, Baier G
The Nuclear Orphan Receptor NR2F6 Suppresses Lymphocyte Activation and T Helper 17-Dependent Autoimmunity.
Immunity. 2008 Aug;29(2):205-16

  Letschka T, Kollmann V, Pfeifhofer-Obermair C, Lutz-Nicoladoni C, Obermair G, Fresser F, Leitges M, Hermann-Kleiter N, Kaminski S, Baier G
PKCtheta selectively controls the adhesion-stimulating molecule Rap1.
Blood. 2008 Dec 1;112(12):4617-27. Epub 2008 Sep 16

  Hermann-Kleiter N, Gruber T, Lutz-Nicoladoni C, Thuille N, Fresser F, Labi V, Schiefermeier N, Warnecke M, Huber L, Villunger A, Eichele G, Kaminski S, Baier G
The Nuclear Orphan Receptor NR2F6 Suppresses Lymphocyte Activation and T Helper 17-Dependent Autoimmunity.

Immunity. 2008 Aug;29(2):205-16

  Hermann-Kleiter N, Thuille N, Pfeifhofer C, Gruber T, Schäfer M, Zitt C, Hatzelmann A, Schudt C, Leitges M, Baier G
PKCθ and PKA are antagonistic partners in NF-AT activation of CD3+ T lymphocytes.
Blood. 15 June 2006 Jun 15;107(12):4841-8.