The nervous system and the immune system are the two large sensory units of the body, which perpetually monitor tissue integrity and mount effector responses upon disturbance of tissue hemostasis. However, how these two sensory systems exchange information and coordinate tissue protective responses remains elusive. Our research has recently exposed signaling pathways, by which the nervous system regulates innate lymphoid cells (ILCs) and type 2 immune responses via the production of neuropeptides (neuromedin U) and neurotransmitters (norepinephrine). ILCs are an emerging population of tissue-resident innate immune cells enriched at mucosal barriers, which can mount either protective or detrimental immune response at barrier surfaces. While we begin to understand some of the tissue-specific cues, which regulate immune activation at barrier surfaces, neuronal regulation of immune responses is still almost a black box. In order to systematically investigate neuro-immune crosstalk at mucosal surfaces in health and disease, we have developed elegant genetic tools, which allow experimental manipulation of neurons and ILCs. Taken together, combing cutting-edge technologies in the fields of immunology, neuroscience and genomics, will enable us to conceptually understand neuro-immune interaction and uncover signaling pathways that have the potential to be therapeutically harnessed.
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1. Gronke, K., P.P. Hernandez, J. Zimmermann, C.S.N. Klose, M. Kofoed-Branzk, F. Guendel, M. Witkowski, C. Tizian, L. Amann, F. Schumacher, H. Glatt, A. Triantafyllopoulou, and A. Diefenbach. 2019. Interleukin-22 protects intestinal stem cells against genotoxic stress. Nature. 566:249-253.
2. Klose, C.S., and D. Artis. 2018. Neuronal regulation of innate lymphoid cells. Current opinion in immunology. 56:94-99.
3. Chu, C., S. Moriyama, Z. Li, L. Zhou, A.L. Flamar, C.S.N. Klose, J.B. Moeller, G.G. Putzel, D.R. Withers, G.F. Sonnenberg, & D. Artis, 2018. Anti-microbial Functions of Group 3 Innate Lymphoid Cells in Gut-Associated Lymphoid Tissues Are Regulated by G-Protein-Coupled Receptor 183. Cell reports. 23, 3750-3758.
4. Rafei-Shamsabadi, D.A., S. van de Poel, B. Dorn, S. Kunz, S.F. Martin, C.S.N. Klose, S.J. Arnold, Y. Tanriver, K. Ebert, A. Diefenbach, T.Y.F. Halim, A.N.J. McKenzie, and T. Jakob. 2018. Lack of Type 2 Innate Lymphoid Cells Promotes a Type I-Driven Enhanced Immune Response in Contact Hypersensitivity. The Journal of investigative dermatology. 138:1962-1972.
5. Moriyama, S., J.R. Brestoff, A.L. Flamar, J.B. Moeller, C.S.N. Klose, L.C. Rankin, N.A. Yudanin, L.A. Monticelli, G.G. Putzel, H.R. Rodewald, and D. Artis. 2018. beta2-adrenergic receptor-mediated negative regulation of group 2 innate lymphoid cell responses. Science. 359:1056-1061.
6. Klose, C.S.*, J.F. Hummel*, L. Faller, Y. d’Hargues, K. Ebert, and Y. Tanriver. 2018. A committed postselection precursor to natural TCRαβ+ intraepithelial lymphocytes. Mucosal immunology. 11, 333-344.
7. Wallrapp, A., S.J. Riesenfeld, P.R. Burkett, R.E. Abdulnour, J. Nyman, D. Dionne, M. Hofree, M.S. Cuoco, C. Rodman, D. Farouq, B.J. Haas, T.L. Tickle, J.J. Trombetta, P. Baral, C.S. Klose, T. Mahlakoiv, D. Artis, O. Rozenblatt-Rosen, I.M. Chiu, B.D. Levy, M.S. Kowalczyk, A. Regev, and V.K. Kuchroo. 2017. The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation. Nature. 549:351-356.
8. Klose, C.S., T. Mahlakoiv, J.B. Moeller, L.C. Rankin, A.L. Flamar, H. Kabata, L.A. Monticelli, Moriyama, G.G. Putzel, N. Rakhilin, X. Shen, E. Kostenis, G.M. Konig, T. Senda, D. Carpenter, D.L. Farber, and D. Artis. 2017. The neuropeptide neuromedin U stimulates innate lymphoid cells and type 2 inflammation. Nature. 549:282-286.
9. Nussbaum, K., S.H. Burkhard, I. Ohs, F. Mair, C.S. Klose, S.J. Arnold, A. Diefenbach, S. Tugues, and B. Becher. 2017. Tissue microenvironment dictates the fate and tumor-suppressive function of type 3 ILCs. The Journal of experimental medicine. 214:2331-2347.
10. Klose, C.S., and D. Artis. 2016. Innate lymphoid cells as regulators of immunity, inflammation and tissue homeostasis. Nature immunology. 17:765-774.
11. Klose, C.S.*, K. Blatz*, Y. d’Hargues, P.P. Hernandez, M. Kofoed-Nielsen, J.F. Ripka, K. Ebert, S.J. Arnold, A. Diefenbach, E. Palmer, and Y. Tanriver. 2014. The Transcription Factor T-bet Is Induced by IL-15 and Thymic Agonist Selection and Controls CD8αα+ Intraepithelial Lymphocyte Development. Immunity. 41:230-243.
12. Klose, C.S., and A. Diefenbach. 2014. Transcription factors controlling innate lymphoid cell fate decisions. Current topics in microbiology and immunology. 381:215-255.
13. Klose, C.S.*, M. Flach*, L. Mohle, L. Rogell, T. Hoyler, K. Ebert, C. Fabiunke, D. Pfeifer, V. Sexl, D. Fonseca-Pereira, R.G. Domingues, H. Veiga-Fernandes, S.J. Arnold, M. Busslinger, I.R. Dunay, Y. Tanriver, and A. Diefenbach. 2014. Differentiation of Type 1 ILCs from a Common Progenitor to All Helper-like Innate Lymphoid Cell Lineages. Cell. 157:340-356.
14. Klose, C.S., E.A. Kiss, V. Schwierzeck, K. Ebert, T. Hoyler, Y. d’Hargues, N. Goppert, A.L. Croxford, A. Waisman, Y. Tanriver, and A. Diefenbach. 2013. A T-bet gradient controls the fate and function of CCR6– RORγt+ innate lymphoid cells. Nature. 494:261-265.
15. Klose, C.S., T. Hoyler, E.A. Kiss, Y. Tanriver, and A. Diefenbach. 2012. Transcriptional control of innate lymphocyte fate decisions. Current opinion in immunology. 24:290-296.
16. Hoyler, T.*, C.S. Klose*, A. Souabni, A. Turqueti-Neves, D. Pfeifer, E.L. Rawlins, D. Voehringer, M. Busslinger, and A. Diefenbach. 2012. The Transcription Factor GATA-3 Controls Cell Fate and Maintenance of Type 2 Innate Lymphoid Cells. Immunity. 37:634-648.
17. Lang, P.A., K.S. Lang, H.C. Xu, M. Grusdat, I.A. Parish, M. Recher, A.R. Elford, S. Dhanji, N. Shaabani, C.W. Tran, D. Dissanayake, R. Rahbar, M. Ghazarian, A. Brustle, J. Fine, P. Chen, C.T. Weaver, C. Klose, A. Diefenbach, D. Haussinger, J.R. Carlyle, S.M. Kaech, T.W. Mak, and P.S. Ohashi. 2012. Natural killer cell activation enhances immune pathology and promotes chronic infection by limiting CD8+ T-cell immunity. Proceedings of the National Academy of Sciences of the United States of America. 109:1210-1215
18. van de Weyer, P.S., M. Muehlfeit, C. Klose, J.V. Bonventre, G. Walz, and E.W. Kuehn. 2006. A highly conserved tyrosine of Tim-3 is phosphorylated upon stimulation by its ligand galectin-9. Biochemical and biophysical research communications. 351:571-576.
* co-first authors