The adaptive immune system responds to pathogen infection by mobilizing distinct effector modules, namely type 1 (IFN-γ TNF), type 2 (IL-4, IL-5 and IL-13) and type 17 (IL-17, IL-22), which are tailored to eliminate different infectious agents. In T cells, such inflammatory programs induced by the T cell receptor (TCR) together with distinct cytokines and/or environmental signals, can be epigenetically imprinted and memorized. While the imprinting of inflammatory signatures enables a faster and stronger response during secondary infection, it also facilitates the induction and perpetuation of chronic inflammation, a hallmark of rheumatic diseases.
Recently, it appeared evident that emerging innate cell subsets lacking the TCR and collectively known as innate lymphoid cells (ILCs), exhibit a similar heterogeneity of effector modules, which can be activated in the course of inflammation. The ILC family includes three main groups of cells: group 1 ILCs, including cytotoxic Natural Killer (NK) cells and the IFN-γ producing ILC1; ILC2 producing IL-13/IL-5, and ILC3 secreting IL-22/IL-17. These cells play a dual role during immune responses by on the one hand exhibiting pro-inflammatory functions and worsening chronic inflammation and on the other hand displaying tissue repair functions.
The signals and innate receptors instructing the different effector programs and their execution in ILCs remain largely unknown. Such innate sensors could also enhance effector functions in T cells, thus promoting inflammation in a TCR-independent fashion. Moreover, it is still unclear whether these inflammatory programs can be also memorized and imprinted in ILCs, thus possibly perpetuating chronic inflammation.
Therefore, our main research focus is devoted to study the innate modules and triggers employed by ILCs and T cells to initiate and maintain inflammation in a TCR-independent fashion and to understand, whether distinct inflammatory programs can be imprinted in ILCs to promote rheumatic diseases. The identification of alternative triggering and perpetuators of inflammation will provide us with new potential targets for the treatment of chronic rheumatic diseases.
Paclik D, Stehle C, Lahmann A, Hutloff A, Romagnani C. ICOS regulates the pool of group 2 innate lymphoid cells under homeostatic and inflammatory conditions in mice. Eur J Immunol. 2015 Oct;45(10):2766-72. Equal contribution (I.F. 4.518)
Montaldo E, Teixeira-Alves LG, Glatzer T, Hamann W, Babic M, Paclik D, Stölzel K, Gröne J, Lozza L, Juelke K, Matzmohr N, Loiacono F, Petronelli P, Huntington ND, Moretta L, Mingari MC and Romagnani C. Human RORgt+ CD34+ cells are lineage-specified progenitors of group 3 RORgt+ innate lymphoid cells. Immunity. 2014 Dec 18;41(6):988-1000. (I.F. 21)
Luetke-Eversloh M, Hammer Q, Durek P, Nordström K, Gasparoni G, Pink M, Hamann A, Walter J, Chang HD, Dong J and Romagnani C. Human Cytomegalovirus Drives Epigenetic Imprinting of the IFNG Locus in NKG2Chi Natural Killer Cells. PLoS Pathog. 2014 Oct 16;10(10):e1004441. (I.F. 8.057)
Killig M, Friedrichs B, Meisig J, Gentilini C, Blüthgen N, Loddenkemper C, Labopin M, Basara N, Pfrepper C, Niederwieser DW, Uharek L, Romagnani C. Tracking in vivo dynamics of NK cells transferred in patients undergoing stem cell transplantation. Eur J Immunol. 2014 Sep;44(9):2822-34. Equal contribution (I.F. 4.518)
Luetke-Eversloh M, Cicek BB, Siracusa F, Thom JT, Hamann A, Frischbutter S, Baumgrass R, Chang HD, Thiel A, Dong J, Romagnani C. NK cells gain higher IFN-γ competence during terminal differentiation. Eur J Immunol. 2014 Jul;44(7):2074-84. (I.F. 4.518)
Dr. Chiara Romagnani
Dr. Daniela Paclik
Dr. Marina Babic Câc
Dr. Kerstin Juelke
Hutloff A, Hamann A, Baumgrass R, Hyun-Dong Chang | DRFZ, Berlin
Thiel A | Berlin-Brandenburg Center for Regenerative Therapies, Charité Universitätsmedizin, Berlin
Bluethgen N, Meisig J | Medical Systems Biology, Charité Universitätsmedizin, Berlin
Gröne J | Chirurgische Klinik und Hochschulambulanz I, Charité Universitätsmedizin Berlin
Kühl A | Charité – Universitätsmedizin Berlin, iPATH Berlin, RCIS, Berlin, Deutschland
Stölzel K | Hals-Nasen-Ohrenklinik und Poliklinik, Charité Universitätsmedizin CBF, Berlin
Uharek L, Friederichs B | Hämatologie, Charité Universitätsmedizin CBF, Berlin
Seidl R | HNO-Klinik, Unfallkrankenhaus, Berlin Walter J | Saarland University, Saarbrücken
Schüler T | Otto-von-Guericke-Universität Magdeburg
Vivier E | Centre d’Immunologie de Marseille-Luminy, France
Moretta L | Istituto Gaslini, Genova, Italy
Huntington N | The University of Melbourne