Inositol-triphosphate 3-kinase B promotes calcium mobilization and the inflammatory activity of dendritic cells.

[en] Innate immune responses to Gram-negative bacteria depend on the recognition of lipopolysaccharide (LPS) by a receptor complex that includes CD14 and TLR4. In dendritic cells (DCs), CD14 enhances the activation not only of TLR4 but also that of the NFAT family of transcription factors, which suppresses cell survival and promotes the production of inflammatory mediators. NFAT activation requires Ca2+ mobilization. In DCs, Ca2+ mobilization in response to LPS depends on phospholipase C γ2 (PLCγ2), which produces inositol 1,4,5-trisphosphate (IP3). Here, we showed that the IP3 receptor 3 (IP3R3) and ITPKB, a kinase that converts IP3 to inositol 1,3,4,5-tetrakisphosphate (IP4), were both necessary for Ca2+ mobilization and NFAT activation in mouse and human DCs. A pool of IP3R3 was located on the plasma membrane of DCs, where it colocalized with CD14 and ITPKB. Upon LPS binding to CD14, ITPKB was required for Ca2+ mobilization through plasma membrane-localized IP3R3 and for NFAT nuclear translocation. Pharmacological inhibition of ITPKB in mice reduced both LPS-induced tissue swelling and the severity of inflammatory arthritis to a similar extent as that induced by the inhibition of NFAT using nanoparticles that delivered an NFAT-inhibiting peptide specifically to phagocytic cells. Our results suggest that ITPKB may represent a promising target for anti-inflammatory therapies that aim to inhibit specific DC functions.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Marongiu, L

Mingozzi, F

Cigni, C

Marzi, R

Di Gioia, M

Garrè, M

Parazzoli, D

Sironi, L

Collini, M

Sakaguchi, R

More authors (11 more)

Language :

English

Title :

Inositol-triphosphate 3-kinase B promotes calcium mobilization and the inflammatory activity of dendritic cells.

Publication date :

2021

Journal title :

Science Signaling

ISSN :

1945-0877

eISSN :

1937-9145

Publisher :

American Association for the Advancement of Science, Washington, United States - District of Columbia

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 01 April 2021

Statistics

Number of views

67 (9 by ULiège)

Number of downloads

14 (2 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

Bibliography

R. Ostuni, I. Zanoni, F. Granucci, Deciphering the complexity of Toll-like receptor signaling. Cell. Mol. Life Sci. 67, 4109-4134 (2010).
S. Herbst, A. Shah, M. Mazon Moya, V. Marzola, B. Jensen, A. Reed, M. A. Birrell, S. Saijo, S. Mostowy, S. Shaunak, D. Armstrong-James, Phagocytosis-dependent activation of a TLR9-BTK-calcineurin-NFAT pathway co-ordinates innate immunity to Aspergillus fumigatus. EMBO Mol. Med. 7, 240-258 (2015).
I. Zanoni, R. Ostuni, G. Capuano, M. Collini, M. Caccia, A. E. Ronchi, M. Rocchetti, F. Mingozzi, M. Foti, G. Chirico, B. Costa, A. Zaza, P. Ricciardi-Castagnoli, F. Granucci, CD14 regulates the dendritic cell life cycle after LPS exposure through NFAT activation. Nature 460, 264-268 (2009).
H. S. Goodridge, R. M. Simmons, D. M. Underhill, Dectin-1 stimulation by Candida albicans yeast or zymosan triggers NFAT activation in macrophages and dendritic cells. J. Immunol. 178, 3107-3115 (2007).
M. J. Robinson, F. Osorio, M. Rosas, R. P. Freitas, E. Schweighoffer, O. Gross, J. S. Verbeek, J. Ruland, V. Tybulewicz, G. D. Brown, L. F. Moita, P. R. Taylor, C. Reis e Sousa, Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infection. J. Exp. Med. 206, 2037-2051 (2009).
A. Vandewalle, E. Tourneur, M. Bens, C. Chassin, C. Werts, Calcineurin/NFAT signaling and innate host defence: A role for NOD1-mediated phagocytic functions. Cell Commun. Sig. 12, 8 (2014).
M. B. Greenblatt, A. Aliprantis, B. Hu, L. H. Glimcher, Calcineurin regulates innate antifungal immunity in neutrophils. J. Exp. Med. 207, 923-931 (2010).
W. Santus, S. Barresi, F. Mingozzi, A. Broggi, I. Orlandi, G. Stamerra, M. Vai, A. M. Martorana, A. Polissi, J. R. Kohler, N. Liu, I. Zanoni, F. Granucci, Skin infections are eliminated by cooperation of the fibrinolytic and innate immune systems. Sci. Immunol. 2, eaan2725 (2017).
T. Zelante, A. Y. W. Wong, A. Mencarelli, S. Foo, F. Zolezzi, B. Lee, M. Poidinger, P. Ricciardi-Castagnoli, J. Fric, Impaired calcineurin signaling in myeloid cells results in downregulation of pentraxin-3 and increased susceptibility to aspergillosis. Mucosal Immunol. 10, 470-480 (2017).
Z. Pang, R. D. Junkins, A. J. MacNeil, C. McCormick, Z. Cheng, W. M. Chen, T. J. Lin, The calcineurin-NFAT axis contributes to host defense during Pseudomonas aeruginosa lung infection. J. Leukoc. Biol. 102, 1461-1469 (2017).
A. Mencarelli, H. J. Khameneh, J. Fric, M. Vacca, S. El Daker, B. Janela, J. P. Tang, S. Nabti, A. Balachander, T. S. Lim, F. Ginhoux, P. Ricciardi-Castagnoli, A. Mortellaro, Calcineurinmediated IL-2 production by CD11chighMHCII+ myeloid cells is crucial for intestinal immune homeostasis. Nat. Commun. 9, 1102 (2018).
I. Zanoni, R. Ostuni, S. Barresi, M. Di Gioia, A. Broggi, B. Costa, R. Marzi, F. Granucci, CD14 and NFAT mediate lipopolysaccharide-induced skin edema formation in mice. J. Clin. Invest. 122, 1747-1757 (2012).
I. Zanoni, F. Granucci, Regulation and dysregulation of innate immunity by NFAT signaling downstream of pattern recognition receptors (PRRs). Eur. J. Immunol. 42, 1924-1931 (2012).
Z. Liu, J. Lee, S. Krummey, W. Lu, H. Cai, M. J. Lenardo, The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease. Nat. Immunol. 12, 1063-1070 (2011).
A. Yarilina, K. Xu, J. Chen, L. B. Ivashkiv, TNF activates calcium-nuclear factor of activated T cells (NFAT)c1 signaling pathways in human macrophages. Proc. Natl. Acad. Sci. U.S.A. 108, 1573-1578 (2011).
M. Prakriya, R. S. Lewis, Store-operated calcium channels. Physiol. Rev. 95, 1383-1436 (2015).
P. J. Shaw, S. Feske, Regulation of lymphocyte function by ORAI and STIM proteins in infection and autoimmunity. J. Physiol. 590, 4157-4167 (2012).
S. Srikanth, Y. Gwack, Orai1-NFAT signalling pathway triggered by T cell receptor stimulation. Mol. Cells 35, 182-194 (2013).
T. Hofmann, A. G. Obukhov, M. Schaefer, C. Harteneck, T. Gudermann, G. Schultz, Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature 397, 259-263 (1999).
J. W. Putney, PLC-gamma: An old player has a new role. Nat. Cell Biol. 4, E280-E281 (2002).
R. L. Patterson, D. Boehning, S. H. Snyder, Inositol 1, 4, 5-trisphosphate receptors as signal integrators. Annu. Rev. Biochem. 73, 437-465 (2004).
S. Feske, Calcium signalling in lymphocyte activation and disease. Nat. Rev. Immunol. 7, 690-702 (2007).
T. Nakagawa, H. Okano, T. Furuichi, J. Aruga, K. Mikoshiba, The subtypes of the mouse inositol 1, 4, 5-trisphosphate receptor are expressed in a tissue-specific and developmentally specific manner. Proc. Natl. Acad. Sci. U.S.A. 88, 6244-6248 (1991).
C. A. Ross, S. K. Danoff, M. J. Schell, S. H. Snyder, A. Ullrich, Three additional inositol 1, 4, 5-trisphosphate receptors: Molecular cloning and differential localization in brain and peripheral tissues. Proc. Natl. Acad. Sci. U.S.A. 89, 4265-4269 (1992).
M. Matsumoto, E. Nagata, Type 1 inositol 1, 4, 5-trisphosphate receptor knock-out mice: Their phenotypes and their meaning in neuroscience and clinical practice. J. Mol. Med. (Berl) 77, 406-411 (1999).
T. Vervloessem, D. I. Yule, G. Bultynck, J. B. Parys, The type 2 inositol 1, 4, 5-trisphosphate receptor, emerging functions for an intriguing Ca2+-release channel. Biochim. Biophys. Acta 1853, 1992-2005 (2015).
T. Tamura, M. Hashimoto, J. Aruga, Y. Konishi, M. Nakagawa, T. Ohbayashi, M. Shimada, K. Mikoshiba, Promoter structure and gene expression of the mouse inositol 1, 4, 5-trisphosphate receptor type 3 gene. Gene 275, 169-176 (2001).
T. Miyakawa, A. Maeda, T. Yamazawa, K. Hirose, T. Kurosaki, M. Iino, Encoding of Ca2+ signals by differential expression of IP3 receptor subtypes. EMBO J. 18, 1303-1308 (1999).
D.-O. Mak, S. McBride, J. K. Foskett, Regulation by Ca2+ and inositol 1, 4, 5-trisphosphate (InsP3) of single recombinant type 3 InsP3 receptor channels. Ca2+ activation uniquely distinguishes types 1 and 3 insp3 receptors. J. Gen. Physiol. 117, 435-446 (2001).
R. E. Hagar, A. D. Burgstahler, M. H. Nathanson, B. E. Ehrlich, Type III InsP3 receptor channel stays open in the presence of increased calcium. Nature 396, 81-84 (1998).
M. Vaeth, I. Zee, A. R. Concepcion, M. Maus, P. Shaw, C. Portal-Celhay, A. Zahra, L. Kozhaya, C. Weidinger, J. Philips, D. Unutmaz, S. Feske, Ca2+ signaling but not store-operated Ca2+ entry is required for the function of macrophages and dendritic cells. J. Immunol. 195, 1202-1217 (2015).
F. Di Virgilio, Purinergic mechanism in the immune system: A signal of danger for dendritic cells. Purinergic Signal. 1, 205-209 (2005).
S. Hsu, P. J. O'Connell, V. A. Klyachko, M. N. Badminton, A. W. Thomson, M. B. Jackson, D. E. Clapham, G. P. Ahern, Fundamental Ca2+ signaling mechanisms in mouse dendritic cells: CRAC is the major Ca2+ entry pathway. J. Immunol. 166, 6126-6133 (2001).
C. Winzler, P. Rovere, M. Rescigno, F. Granucci, G. Penna, L. Adorini, V. S. Zimmermann, J. Davoust, P. Ricciardi-Castagnoli, Maturation stages of mouse dendritic cells in growth factor-dependent long-term cultures. J. Exp. Med. 185, 317-328 (1997).
J. Ishikawa, K. Ohga, T. Yoshino, R. Takezawa, A. Ichikawa, H. Kubota, T. Yamada, A pyrazole derivative, YM-58483, potently inhibits store-operated sustained Ca2+ influx and IL-2 production in T lymphocytes. J. Immunol. 170, 4441-4449 (2003).
T. Yoshino, J. Ishikawa, K. Ohga, T. Morokata, R. Takezawa, H. Morio, Y. Okada, K. Honda, T. Yamada, YM-58483, a selective CRAC channel inhibitor, prevents antigen-induced airway eosinophilia and late phase asthmatic responses via Th2 cytokine inhibition in animal models. Eur. J. Pharmacol. 560, 225-233 (2007).
K. Ohga, R. Takezawa, Y. Arakida, Y. Shimizu, J. Ishikawa, Characterization of YM-58483/ BTP2, a novel store-operated Ca2+ entry blocker, on T cell-mediated immune responses in vivo. Int. Immunopharmacol. 8, 1787-1792 (2008).
R. Takezawa, H. Cheng, A. Beck, J. Ishikawa, P. Launay, H. Kubota, J. P. Kinet, A. Fleig, T. Yamada, R. Penner, A pyrazole derivative potently inhibits lymphocyte Ca2+ influx and cytokine production by facilitating transient receptor potential melastatin 4 channel activity. Mol. Pharmacol. 69, 1413-1420 (2006).
J. Helft, J. Bottcher, P. Chakravarty, S. Zelenay, J. Huotari, B. U. Schraml, D. Goubau, C. Reis e Sousa, GM-CSF mouse bone marrow cultures comprise a heterogeneous population of CD11c+MHCII+ macrophages and dendritic cells. Immunity 42, 1197-1211 (2015).
O. Dellis, S. G. Dedos, S. C. Tovey, R. Taufiq-Ur-Rahman, S. J. Dubel, C. W. Taylor, Ca2+ entry through plasma membrane IP3 receptors. Science 313, 229-233 (2006).
A. C. Villani, R. Satija, G. Reynolds, S. Sarkizova, K. Shekhar, J. Fletcher, M. Griesbeck, A. Butler, S. Zheng, S. Lazo, L. Jardine, D. Dixon, E. Stephenson, E. Nilsson, I. Grundberg, D. McDonald, A. Filby, W. Li, P. L. De Jager, O. Rozenblatt-Rosen, A. A. Lane, M. Haniffa, A. Regev, N. Hacohen, Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors. Science 356, eaah4573 (2017).
C. A. Dutertre, E. Becht, S. E. Irac, A. Khalilnezhad, V. Narang, S. Khalilnezhad, P. Y. Ng, L. L. van den Hoogen, J. Y. Leong, B. Lee, M. Chevrier, X. M. Zhang, P. J. A. Yong, G. Koh, J. Lum, S. W. Howland, E. Mok, J. Chen, A. Larbi, H. K. K. Tan, T. K. H. Lim, P. Karagianni, A. G. Tzioufas, B. Malleret, J. Brody, S. Albani, J. van Roon, T. Radstake, E. W. Newell, F. Ginhoux, Single-cell analysis of human mononuclear phagocytes reveals subsetdefining markers and identifies circulating inflammatory dendritic cells. Immunity 51, 573-589.e8 (2019).
M. Rusconi, F. Gerardi, W. Santus, A. Lizio, V. A. Sansone, C. Lunetta, I. Zanoni, F. Granucci, Inflammatory role of dendritic cells in amyotrophic lateral sclerosis revealed by an analysis of patients' peripheral blood. Sci. Rep. 7, 7853 (2017).
K. Takazawa, J. Perret, J. E. Dumont, C. Erneux, Molecular cloning and expression of a new putative inositol 1, 4, 5-trisphosphate 3-kinase isoenzyme. Biochem. J. 278 (Pt 3), 883-886 (1991).
A. T. Miller, C. Dahlberg, M. L. Sandberg, B. G. Wen, D. R. Beisner, J. A. Hoerter, A. Parker, C. Schmedt, M. Stinson, J. Avis, C. Cienfuegos, M. McPate, P. Tranter, M. Gosling, P. J. Groot-Kormelink, J. Dawson, S. Pan, S.-S. Tian, H. M. Seidel, M. P. Cooke, Inhibition of the inositol kinase Itpkb augments calcium signaling in lymphocytes and reveals a novel strategy to treat autoimmune disease. PLOS ONE 10, e0131071 (2015).
B. G. Wen, M. T. Pletcher, M. Warashina, S. H. Choe, N. Ziaee, T. Wiltshire, K. Sauer, M. P. Cooke, Inositol (1, 4, 5) trisphosphate 3 kinase B controls positive selection of T cells and modulates Erk activity. Proc. Natl. Acad. Sci. U.S.A. 101, 5604-5609 (2004).
Y. Jia, F. Loison, H. Hattori, Y. Li, C. Erneux, S. Y. Park, C. Gao, L. Chai, L. E. Silberstein, S. Schurmans, H. R. Luo, Inositol trisphosphate 3-kinase B (InsP3KB) as a physiological modulator of myelopoiesis. Proc. Natl. Acad. Sci. U.S.A. 105, 4739-4744 (2008).
A. Scoumanne, P. Molina-Ortiz, D. Monteyne, D. Perez-Morga, C. Erneux, S. Schurmans, Specific expression and function of inositol 1, 4, 5-trisphosphate 3-kinase C (ITPKC) in wild type and knock-out mice. Adv. Biol. Regul. 62, 1-10 (2016).
V. Pouillon, Y. Marechal, C. Frippiat, C. Erneux, S. Schurmans, Inositol 1, 4, 5-trisphosphate 3-kinase B (Itpkb) controls survival, proliferation and cytokine production in mouse peripheral T cells. Adv. Biol. Regul. 53, 39-50 (2013).
A. T. Miller, D. R. Beisner, D. Liu, M. P. Cooke, Inositol 1, 4, 5-trisphosphate 3-kinase B is a negative regulator of BCR signaling that controls B cell selection and tolerance induction. J. Immunol. 182, 4696-4704 (2009).
Y. Marechal, S. Queant, S. Polizzi, V. Pouillon, S. Schurmans, Inositol 1, 4, 5-trisphosphate 3-kinase B controls survival and prevents anergy in B cells. Immunobiology 216, 103-109 (2011).
R. Hascakova-Bartova, V. Pouillon, V. Dewaste, C. Moreau, C. Jacques, G. Banting, S. Schurmans, C. Erneux, Identification and subcellular distribution of endogenous Ins(1, 4, 5)P(3) 3-kinase B in mouse tissues. Biochem. Biophys. Res. Commun. 323, 920-925 (2004).
V. Dewaste, C. Moreau, F. De Smedt, F. Bex, H. De Smedt, F. Wuytack, L. Missiaen, C. Erneux, The three isoenzymes of human inositol-1, 4, 5-trisphosphate 3-kinase show specific intracellular localization but comparable Ca2+ responses on transfection in COS-7 cells. Biochem. J. 374, 41-49 (2003).
R. Sakaguchi, K. Tainaka, N. Shimada, S. Nakano, M. Inoue, S. Kiyonaka, Y. Mori, T. Morii, An in vivo fluorescent sensor reveals intracellular ins(1, 3, 4, 5)P4 dynamics in single cells. Angew. Chem. Int. Ed. Engl. 49, 2150-2153 (2010).
J. Aramburu, M. B. Yaffe, C. Lopez-Rodriguez, L. C. Cantley, P. G. Hogan, A. Rao, Affinity-driven peptide selection of an NFAT inhibitor more selective than cyclosporin A. Science 285, 2129-2133 (1999).
L. Fiandra, S. Mazzucchelli, C. De Palma, M. Colombo, R. Allevi, S. Sommaruga, E. Clementi, M. Bellini, D. Prosperi, F. Corsi, Assessing the in vivo targeting efficiency of multifunctional nanoconstructs bearing antibody-derived ligands. ACS Nano 7, 6092-6102 (2013).
M. Colombo, S. Sommaruga, S. Mazzucchelli, L. Polito, P. Verderio, P. Galeffi, F. Corsi, P. Tortora, D. Prosperi, Site-specific conjugation of ScFvs antibodies to nanoparticles by bioorthogonal strain-promoted alkyne-nitrone cycloaddition. Angew. Chem. Int. Ed. Engl. 51, 496-499 (2012).
C.-A. Lin, R. A. Sperling, J. K. Li, T.-Y. Yang, P.-Y. Li, M. Zanella, W. H. Chang, W. J. Parak, Design of an amphiphilic polymer for nanoparticle coating and functionalization. Small 4, 334-341 (2008).
S. Mazzucchelli, M. Colombo, P. Verderio, E. Rozek, F. Andreata, E. Galbiati, P. Tortora, F. Corsi, D. Prosperi, Orientation-controlled conjugation of haloalkane dehalogenase fused homing peptides to multifunctional nanoparticles for the specific recognition of cancer cells. Angew. Chem. Int. Ed. Engl. 52, 3121-3125 (2013).
K. S. Nandakumar, R. Holmdahl, Efficient promotion of collagen antibody induced arthritis (CAIA) using four monoclonal antibodies specific for the major epitopes recognized in both collagen induced arthritis and rheumatoid arthritis. J. Immunol. Methods 304, 126-136 (2005).
A. J. Gerth, C. T. Pham, S. L. Peng, Regulation of the symmetry and intensity of immune complex-mediated synovitis by nuclear factor of activated T cells. Arthritis Rheum. 50, 3392-3395 (2004).
S. Feske, H. Wulff, E. Y. Skolnik, Ion channels in innate and adaptive immunity. Annu. Rev. Immunol. 33, 291-353 (2015).
I. Zanoni, C. Bodio, A. Broggi, R. Ostuni, M. Caccia, M. Collini, A. Venkatesh, R. Spreafico, G. Capuano, F. Granucci, Similarities and differences of innate immune responses elicited by smooth and rough LPS. Immunol. Lett. 142, 41-47 (2012).
D. A. Fadool, B. W. Ache, Plasma membrane inositol 1, 4, 5-trisphosphate-activated channels mediate signal transduction in lobster olfactory receptor neurons. Neuron 9, 907-918 (1992).
A. A. Khan, J. P. Steiner, M. G. Klein, M. F. Schneider, S. H. Snyder, IP3 receptor: Localization to plasma membrane of T cells and cocapping with the T cell receptor. Science 257, 815-818 (1992).
G. Guillemette, T. Balla, A. J. Baukal, K. J. Catt, Characterization of inositol 1, 4, 5-trisphosphate receptors and calcium mobilization in a hepatic plasma membrane fraction. J. Biol. Chem. 263, 4541-4548 (1988).
C. Dargemont, M. Hilly, M. Claret, J. P. Mauger, Characterization of Ca2+ fluxes in rat liver plasma-membrane vesicles. Biochem. J. 256, 117-124 (1988).
O. Dellis, A. M. Rossi, S. G. Dedos, C. W. Taylor, Counting functional inositol 1, 4, 5-trisphosphate receptors into the plasma membrane. J. Biol. Chem. 283, 751-755 (2008).
D. Leitenberg, Y. Boutin, S. Constant, K. Bottomly, CD4 regulation of TCR signaling and T cell differentiation following stimulation with peptides of different affinities for the TCR. J. Immunol. 161, 1194-1203 (1998).
N. deSouza, J. Cui, M. Dura, T. V. McDonald, A. R. Marks, A function for tyrosine phosphorylation of type 1 inositol 1, 4, 5-trisphosphate receptor in lymphocyte activation. J. Cell Biol. 179, 923-934 (2007).
A. T. Miller, M. Sandberg, Y. H. Huang, M. Young, S. Sutton, K. Sauer, M. P. Cooke, Production of Ins(1, 3, 4, 5)P4 mediated by the kinase Itpkb inhibits store-operated calcium channels and regulates B cell selection and activation. Nat. Immunol. 8, 514-521 (2007).
K. Sauer, M. P. Cooke, Regulation of immune cell development through soluble inositol-1, 3, 4, 5-tetrakisphosphate. Nat. Rev. Immunol. 10, 257-271 (2010).
D. Prosperi, M. Colombo, I. Zanoni, F. Granucci, Drug nanocarriers to treat autoimmunity and chronic inflammatory diseases. Semin, Immunol. 34, 61-67 (2018).
V. Pouillon, R. Hascakova-Bartova, B. Pajak, E. Adam, F. Bex, V. Dewaste, C. Van Lint, O. Leo, C. Erneux, S. Schurmans, Inositol 1, 3, 4, 5-tetrakisphosphate is essential for T lymphocyte development. Nat. Immunol. 4, 1136-1143 (2003).
M. Oh-Hora, M. Yamashita, P. G. Hogan, S. Sharma, E. Lamperti, W. Chung, M. Prakriya, S. Feske, A. Rao, Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance. Nat. Immunol. 9, 432-443 (2008).