Innate Immunity

Identifying innate signals initiating and perpetuating chronic inflammation

Romagnani

Introduction

Chronic inflammatory disorders, especially rheumatic diseases, are triggered and maintained by effector mediators produced by the adaptive immune system, such as T cells and B cells. The adaptive immune system employs three major effector modules, namely type 1 (IFN-γ and TNF), type 2 (IL-4, IL-5 and IL-13) and type 3 or type 17 (IL-17, IL-22), which give rise to distinct inflammatory tissue responses. In T cells, such inflammatory programs are induced by the T cell receptor (TCR) in conjunction with distinct cytokines and/or environmental signals and can be epigenetically imprinted and memorized. While the imprinting of inflammatory signatures enables a faster and stronger response during secondary infection, it facilitates on the other hand 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. 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 sustaining 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

Differentiation of human innate lymphoid cells (ILCs). Juelke K, Romagnani C. Curr Opin Immunol. 2016 Feb;38:75-85. doi: 10.1016/j. coi.2015.11.005. Epub 2015 Dec 17. Review.

Putting the brakes on ILC2 cells. Stehle C, Saikali P, Romagnani C. Nat Immunol. 2016 Jan;17(1):43-4. doi: 10.1038/ni.3353. No abstract available.

ICOS regulates the pool of group 2 innate lymphoid cells under homeostatic and inflammatory conditions in mice. Paclik D, Stehle C, Lahmann A, Hutloff A, Romagnani C. Eur J Immunol. 2015 Oct;45(10):2766-72. doi: 10.1002/eji.201545635. Epub 2015 Aug 31.

Group 3 innate lymphoid cells (ILC3s): Origin, differentiation, and plasticity in humans and mice. Montaldo E, Juelke K, Romagnani C. Eur J Immunol. 2015 Aug;45(8):2171-82. doi: 10.1002/eji.201545598. Epub 2015 Jun 18. Review.

The 3 major types of innate and adaptive cellmediated effector immunity. Annunziato F, Romagnani C, Romagnani S. J Allergy Clin Immunol. 2015 Mar;135(3):626-35. doi: 10.1016/j. jaci.2014.11.001. Review.

Members

Group leader:
Prof. Dr. Chiara Romagnani

Scientists:
Daniela Paclik
Kerstin Juelke
Marina Babic

Ph.D. students:
Quirin Hammer
Christina Stehle
Timo Rückert

MD students

Andre Haubner

Bachelor/Diploma/Master students
Almut Eisele

Student assistant
Yan Dyck

Cooperation partners

Bluethgen N, Medical Systems Biology, Charité Universitätsmedizin, Berlin, Germany

Cerwenka A, German Cancer Research Center (DKFZ), Innate Immunity , Heidelberg, Germany

Geginat J, Istituto Nazionale di Genetica Molecolare, "Romeo ed Enrica Invernizzi", Milan, Italy.

Malmberg KJ, Béziat V, Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.

Moretta A, Pietra G, University of Genova, Italy

Schüler T, Institute of Molecular and Clinical Immunology, Medical Faculty, Otto von Guericke University, Magdeburg, Germany

Schwab JM, Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, Germany

Seidl R, HNO-Klinik, Unfallkrankenhaus, Berlin, Germany

Stölzel K, Hals-Nasen-Ohrenklinik und Poliklinik, Charité Universitätsmedizin CBF, Berlin

Ullrich E, Division of Stem Cell Transplantation and Immunology, Department for Children and Adolescents Medicine, University Hospital Frankfurt, Goethe University, Frankfurt, Germany.

Vivier E, Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, Marseille, France

Walter J, Genetics/Epigenetics, University of Saarland, Saarbrücken, Germany

Prof. 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
Chronic inflammation
Innate lymphoid cells
Innate receptors
Epigenetic imprinting