Innate Immunity

Innate triggers in chronic inflammation

Romagnani

Introduction

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.

Selected Publications

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)

Members

Group leader:
Dr. Chiara Romagnani

Scientists:
Dr. Daniela Paclik
Dr. Marina Babic Câc
Dr. Kerstin Juelke

Ph.D. students:
Quirin Hammer
Christina Stehle

Student
Timo Rückert

Student assistant
Yan Dyck

Cooperation partners

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

Dr. Chiara Romagnani

Deutsches Rheuma-Forschungszentrum Berlin
Innate Immunity
Charitéplatz 1
10117 Berlin
Gemany

Phone +49 (0)30 28460-681
Fax +49 (0)30 28460-603
romagnani@drfz.de

Keywords
ILC
NK cells
Chronic inflammation
Rheumatic diseases