Extracellular and intracellular adenine nucleotides (AN) impact on all central processes in biology and medicine. AN are essential and ubiquitous signaling molecules involved in regulating universal cellular processes, including (i) cell-cell communication and (ii) intracellular signaling.
Unresolved issues regarding the signaling function of extracellular AN in inflammation, e.g. adenosine triphosphate (ATP) or nicotinamide adenine dinucleotide (NAD), relate to the timing and location of their release, their conversion by ecto-enzymes, and their biological role within the balance of inflammatory processes. Likewise, the precise role of intracellular AN second messengers, e.g. nicotinic acid adenine dinucleotide phosphate (NAADP) or 3’,5’-cyclic adenosine monophosphate (cAMP), in the spatio-temporal control of signaling processes by forming or modulating microdomains with their metabolizing enzymes, specific binding proteins or receptors, or target ion channels remains largely unknown.
The central goal of the research consortium is to further our understanding of the regulatory roles of AN and their kinetics in the context of inflammatory diseases. Specific aims relate to (i) modulation of the balance between pro- and anti-inflammatory processes by AN converting ecto-nucleotidases and purinergic receptors, and to (ii) AN-driven intracellular calcium signaling and cAMP signaling in inflammation.
The paper "Short-term dietary changes can result in mucosal and systemic immune depression" was just published @Nature Immunology. In summary, even a short-term change in diet from normal food to fast food diet could compromise immunity and lead to higher susceptibility to bacterial infections. Great teamwork within SFB1328 including 6 projects lead by A14. This paper was also picked up by newpapers (see Zeit-Online)!
Happy to have our paper about Ca2+ microdomains in T cells that depend on adhesion been published @Science Signaling. Great teamwork within SFB1328 including projects A01, A02 and A03. And we made it to the cover!!!
For further announcements see:
Siracusa F, Schaltenberg N, Kumar Y, Lesker TR, Steglich B, Liwinski T, Cortesi F, Frommann L, Diercks BP, Bönisch F, Fischer AW, Scognamiglio P, Pauly MJ, Casar C, Cohen Y, Pelczar P, Agalioti T, Delfs F, Worthmann A, Wahib R, Jagemann B, Mittrücker HW, Kretz O, Guse AH, Izbicki JR, Lassen KG, Strowig T, Schweizer M, Villablanca EJ, Elinav E, Huber S, Heeren J, Gagliani N. Short-term dietary changes can result in mucosal and systemic immune depression. Nat Immunol. 2023 Aug 14.
Weiß M, Hernandez LC, Gil Montoya DC, Löhndorf A, Krüger A, Kopdag M, Uebler L, Landwehr M, Nawrocki M, Huber S, Woelk LM, Werner R, Failla AV, Flügel A, Dupont G, Guse AH, Diercks BP. Adhesion to laminin-1 and collagen IV induces the formation of Ca2+microdomains that sensitize mouse T cells for activation. Sci Signal. 2023 Jun 20;16(790):eabn9405.
Hosang L, Löhndorf A, Dohle W, Rosche A, Marry S, Diercks BP, Müller-Kirschbaum LC, Flügel LT, Potter BVL, Odoardi F, Guse AH, Flügel A. 2-Methoxyestradiol-3,17-O,O-bis-sulfamate inhibits store-operated Ca2+ entry in T lymphocytes and prevents experimental autoimmune encephalomyelitis. Biochim Biophys Acta Mol Cell Res. 2023 Aug;1870(6):119485.
Westphal T, Mader M, Karsten H, Cords L, Knapp M, Schulte S, Hermanussen L, Peine S, Ditt V, Grifoni A, Addo MM, Huber S, Sette A, Lütgehetmann M, Pischke S, Kwok WW, Sidney J, Schulze Zur Wiesch J. Evidence for broad cross-reactivity of the SARS-CoV-2 NSP12-directed CD4+ T-cell response with pre-primed responses directed against common cold coronaviruses. Front Immunol. 2023 May 5;14:1182504
Giannou AD, Kempski J, Zhang T, Lücke J, Shiri AM, Zazara DE, Belios I, Machicote A, Seeger P, Agalioti T, Tintelnot J, Sagebiel A, Tomczak M, Bauditz L, Bedke T, Kocheise L, Mercanoglu B, Fard-Aghaie M, Giorgakis E, Lykoudis PM, Pikouli A, Grass JK, Wahib R, Bardenhagen J, Brunswig B, Heumann A, Ghadban T, Duprée A, Tachezy M, Melling N, Arck PC, Stringa P, Gentilini MV, Gondolesi GE, Nakano R, Thomson AW, Perez D, Li J, Mann O, Izbicki JR, Gagliani N, Maroulis IC, Huber S. IL-22BP controls the progression of liver metastasis in colorectal cancer. Front Oncol. 2023 May 31;13:1170502.