Innate Immunity

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. 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.

Recently, we have described a specific recognition strategy by Natural Killer (NK) cells which, in the absence of rearranged receptors, can detect mutated peptides derived from virus and host. Specific peptide recognition drives activation and expansion of a specialized subset of adaptive NK cells and contributes to determine their imprinting of pro-inflammatory cytokines. This data have important implications for our understanding of non-self and self-recognition by lymphocytes and how its dysregulation can lead to loss of tolerance and autoimmunity. Our data also indicate that innate activating receptors, such as NKG2D, also regulate Th1/Th17 cell-mediated responses in arthritis, thereby identifying innate activating receptors as potential check points and therapeutic targets for inflammatory diseases.

Altogether, the identification of the innate triggers and the specific signals driving the acquisition and the stable imprinting of distinct inflammatory programs in ILCs and T cells will be important to develop potentially new targets for the amelioration of chronic inflammation in rheumatic diseases.

Rapid response to pathogens involves a pool of innate immune effector cells which respond promptly to infection. However, innate cells can differentiate after pathogen encounters and remember past experiences, acquiring memory-like features. We have found that human memory-like natural killer (NK) cells undergo global epigenetic remodelling and expand clonally in response to cytomegalovirus infection.

We seek to identify the mechanisms driving the acquisition, selection and maintenance of public and private clonal memory in human NK cells. Our working hypothesis is that NK cell clonal expansions might increase NK cell fitness and effector potential but also enhance the risk of oncogenic mutations and of inflammatory disorders.

Group leader
Prof. Chiara Romagnani, MD, Phd

Scientists
Dr. Christina Stehle
Dr. Timo Rückert

Ph.D. students
Nils Müller
Christoforos Dimitropoulos
Oliver Knight
Alexandra Forrai
Klara Penkert
Ramon Ranka
Maximilian Mandry (MD/PHD Student)
Maximilian Riedel
Asta Perl
Melissa Quadflieg

Technician
Marion Klemm
Laura Puccio

Coordination
Dr. Svenja Rühland

Andreas Diefenbach, Christoph Klose, Leif Ludwig, Tillmann Kallinich, Anja Hauser, Mir-Farzin Mashreghi, Hyun-Dong Chang, Ahmed Hegazy, Britta Siegmund

Thomas Höfer (DKFZ), Veit Buchholz (TUM), Thomas Schüler (Univ Magdeburg), Georg Gasteiger (Univ Würzburg)

Mario Assenmacher, Miltenyi Biotech

Eric Vivier, (Centre d’Immunologie de Marseille-Luminy,  Marseille), Joseph Sun (MSKCC, NY), Michael Birnbaum (MIT Boston), Caleb Lareau (MSKCC, NY), Domenico Mavilio (Humanitas, Milano)