Innate lymphocytes, including natural killer cells (NK) and recently discovered novel subsets of innate lymphoid cells (ILC) exert key functions in coordinating local immune responses, including the killing of infected cells, the production of hallmark cytokines that orchestrate immune responses, and the secretion of tissue-protective factors. Innate lymphocytes respond rapidly to environmental cues without the need for further differentiation. The ease of activation needs to be balanced by stringent control mechanisms because excessive activation of innate lymphocytes contributes to a loss of tissue function and facilitates inflammatory processes as well as the exacerbation of infection-associated pathologies.
The cellular interactions and the molecular mechanisms governing the regulation and activation of innate lymphocytes are therefore highly relevant for a broad range of physiologic and pathologic immune responses. Current research has largely focused on the role of innate cytokines and alarmins for the homeostasis and function of innate lymphocytes. In addition to their innate effector functions, ILC and NK cells have been found to participate in shaping and regulating adaptive immune responses. Whether the adaptive immune system may in turn contribute to the control of innate lymphocyte function and homeostasis is largely unknown. During our recent work, we have identified novel regulatory interactions between cells of the adaptive immune system and innate lymphocytes mediated by the “adaptive” cytokine IL-2. Our goal is now to determine the cellular mechanisms and the physiological relevance of these interactions using clinically relevant disease models. We are investigating additional pathways through which adaptive and innate lymphocytes may interact, as well as their potential therapeutic implications. Our aim is to understand the context-dependent physiological and pathological functions of innate lymphocytes for immune homeostasis as well as infectious and inflammatory diseases.
Muschaweckh Andreas, Buchholz Veit R., Fellenzer Anne, Hessel Christian, Koenig Paul-Albert, Tao Sha, Tao Ronny, Heikenwaelder Mathias, Busch Dirk H., Korn Thomas, Kastenmueller Wolfgang, Drexler Ingo, Gasteiger Georg Antigen-dependent competition shapes the local repertoire of tissue-resident memory CD8(+) T cells. JOURNAL OF EXPERIMENTAL MEDICINE. 2016; 213(13): 3075-3086
Chinen Takatoshi, Kannan Arun K., Levine Andrew G., Fan Xiying, Klein Ulf, Zheng Ye, Gasteiger Georg, Feng Yongqiang, Fontenot Jason D., Rudensky Alexander Y. An essential role for the IL-2 receptor in T-reg cell function. NATURE IMMUNOLOGY. 2016; 17(11): 1322-1333
Backes Simone, Jaeger Clemens, Dembek Claudia J., Kosinska Anna D., Bauer Tanja, Stephan Ann-Sophie, Dislers Andris, Mutwiri George, Busch Dirk H., Babiuk Lorne A., Gasteiger Georg, Protzer Ulrike. Protein-prime/modified vaccinia virus Ankara vector-boost vaccination overcomes tolerance in high-antigenemic HBV-transgenic mice. VACCINE. 2016; 34(7): 923-932.
Bedoui Sammy, Gebhardt Thomas, Gasteiger Georg, Kastenmueller Wolfgang. Parallels and differences between innate and adaptive lymphocytes. NATURE IMMUNOLOGY. 2016; 17(5): 490-494.
Gasteiger Georg, Ataide Marco, Kastenmueller Wolfgang. Lymph node - an organ for T-cell activation and pathogen defense. IMMUNOLOGICAL REVIEWS. 2016; 271(1): 200-220.
Gasteiger G, Fan D, Dikyi S, Lee SY and Rudensky AY. Tissue residency of innate lymphoid cells in lymphoid and non-lymphoid organs. Science 2015.
Lu LF, Gasteiger G, Yu IS, Chaudhry A, Bos P, Lin L, Zawislak C, Cho S, Sun JC, Lin SW and Rudensky AY. A single miRNA-mRNA interaction affects the immune Response in a context- and cell type specific manner. Immunity 2015; 43(1):52-64.
Gasteiger Georg, Rudensky Alexander Y., Interactions between innate and adaptive lymphocytes. NATURE REVIEWS IMMUNOLOGY. 2014; 14 (9): 631-639.
Gasteiger G, Hemmers S, Bos P, Sun JC, and Rudensky AY. IL-2 dependent adaptive control of NK cell homeostasis. J Exp Med. 2013 Jun 3;210(6):1179-87.
Gasteier G, Hemmers S, FirthMA, Le Floc'h A, Huse M, Sun JC, and Rudensy AY. IL-2 dependent tuning of NK cell sensitivity for target cells controlled by regulatory T cells. J Exp Med. 2013 Jun 3;210(6):1167-78
Feng Y, Arvey A, Chinen T, Van der Veeken J, Gasteger G, and Rudensky AY. Maintenance of regulatory T cell identity by a dedicated cis element in the Foxp3 locus. Cell. 2014 Aug 14;158(4):749-63.
Geiger TL, Abt MC*, Gasteiger G*, van den Brink MR, Pamer EG, Hanash AM, and Sun JC. Nfil3 is crucial for development of innate lymphoid cells and host protection against intestinal pathogens. J Exp Med. 2014 Aug 25;211(9):1723-31.
Daussy C, Faure F, Mayol K, Viel S, Gasteiger G, Charrier E, Bienvenu J, Henry T, Debien E, Hasan UA, Marvel J, Yoh K, Takahasi S, Prinz I, de Bernard S, Buffat L, and Walzer T. T-bet and Eomes instruct the development of two distinct Natural Killer cell lineages in the liver and in the bone marrow. J Exp Med. 2014 Mar 10;211(3):563-77
Firth MA, Madera S, Beaulieu AM Gasteiger G, Castillo EF, Schluns KS, Kubo M, Rothmann PB, and Sun, JC. NK cell homeostasis, antiviral response, and memory are independent of Nfil3. J Exp Med. 2013 Dec 16;210(13):2981-90