Metabolic regulation of human immune responses

Research Area

  • Macrophage- and T-helper-cell-mediated host defense in humans
  • The role of immunometabolism in infectious and non-infectious skin diseases

Research Projects

Our lab studies molecular mechanisms that regulate human immune responses in skin. We are particularly interested in the molecular cross talk between metabolic pathways and immune signaling in macrophages and T helper cells. While during the past years, we have focused on the interaction of steroid hormones, vitamin D and glucocorticoids, and immune signaling, we are now analyzing additional immunometabolic pathways. Current projects concentrate on the role of vitamin D and iron metabolisms in the macrophage host response and the role of core metabolic pathways in driving macrophage and Th cell responses in infectious and non-infectious skin inflammation. We believe that increased knowledge of the immune-metabolic pathways involved in human skin diseases carries excellent potential for future clinical translation.

Group Members

Selected Publications

Knoke K, Rongisch RR, Grzes KM, Schwarz R, Lorenz B, Yogev N, Pearce EL, J Pearce EJ, Kofler DM, Fabri M. Tofacitinib suppresses IL-10/IL-10R signaling and modulates host defense responses in human macrophages. J Invest Dermatol. 2021 Sep 15;S0022-202X(21)02207-7. Online ahead of print.

O'Sullivan D, Stanczak MA, Villa M, Uhl FM, Corrado M, Klein Geltink RI, Sanin DE, Apostolova P, Rana N, Edwards-Hicks J, Grzes KM, Kabat AM, Kyle RL, Fabri M, Curtis JD, Buck MD, Patterson AE, Regina A, Field CS, Baixauli F, Puleston DJ, Pearce EJ, Zeiser R, Pearce EL. Fever supports CD8+ effector T cell responses by promoting mitochondrial translation. Proc Natl Acad Sci. 2021 Jun 22;118(25):e2023752118.

Klein Geltink RI, Edwards-Hicks J, Apostolova P, O'Sullivan D, Sanin DE, Patterson AE, Puleston DJ, Ligthart NAM, Buescher JM, Grzes KM, Kabat AM, Stanczak M, Curtis JD, Hässler F, Uhl FM, Fabri M, Zeiser R, Pearce EJ, Pearce EL. Metabolic conditioning of CD8+ effector T cells for adoptive cell therapy. Nat Metab. 2020 Aug;2(8):703-716.

Kröll P, Knoke K, Steiger J, Fabri M. IFN-gamma promotes but dexamethasone dissociates TLR2/1-induced host responses in human macrophages. J Invest Dermatol. 2019 Feb;139(2):488-491.

de Castro Kroner J, Knoke K, Kofler DM, Steiger J, Fabri M. Glucocorticoids promote intrinsic human Th17 differentiation. J Allergy Clin Immunol. 2018 Nov;142(5):1669-1673.e11.

Batinica M, Stephan A, Steiger J, Tantcheva-Poόr I, Eming SA, Fabri M. Stimulus-dependent NETosis by neutrophils from a Papillon-Lefèvre Syndrome patient. J Eur Acad Dermatol Venereol. 2017 May;31(5):e239-e241.

Stephan A, Batinica M, Steiger J, Hartmann P, Zaucke F, Bloch W, Fabri M. LL37:DNA complexes provide antimicrobial activity against intracellular bacteria in human macrophages. Immunology. 2016 Aug;148(4):420-32.

Steiger J, Stephan A, Inkeles MS, Realegeno S, Bruns H, Kröll P, de Castro Kroner J, Sommer A, Batinica M, Pitzler L, Kalscheuer R, Hartmann P, Plum G, Stenger S, Pellegrini M, Brachvogel B, Modlin RL, Fabri M. Imatinib Triggers Phagolysosome Acidification and Antimicrobial Activity against Mycobacterium bovis Bacille Calmette-Guérin in Glucocorticoid-Treated Human Macrophages. J Immunol. 2016 Jul 1;197(1):222-32.

Fabri M, Stenger S, Shin DM, Yuk JM, Liu PT, Realegeno S, Lee HM, Krutzik SR, Schenk M, Sieling PA, Teles R, Montoya D, Iyer SS, Bruns H, Lewinsohn DM, Hollis BW, Hewison M, Adams JS, Steinmeyer A, Zügel U, Cheng G, Jo EK, Bloom BR, Modlin RL. Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. Sci Transl Med. 2011 Oct 12;3(104):104ra102.

Publications Prof. Dr. Mario Fabri

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