| LI, J., M. RITELLI, C. S. MA, G. RAO, T. HABIB, E. CORVILAIN, S. BOUGARN, S. CYPOWYJ, Lucie GRODECKÁ, R. LEVY, V. BEZIAT, L. SHANG, K. PAYNE, D. T. AVERY, M. MIGAUD, S. BOUCHERIT, S. BOUGHORBEL, A. GUENNOUN, M. CHRABIEH, F. RAPAPORT, B. BIGIO, Y. ITAN, B. BOISSON, V. CORMIER-DAIRE, D. SYX, F. MALFAIT, N. ZOPPI, L. ABEL, Tomáš FREIBERGER, H. C. DIETZ, N. MARR, S. G. TANGYE, M. COLOMBI, J. L. CASANOVA, A. PUEL a C. FIESCHI. Chronic mucocutaneous candidiasis and connective tissue disorder in humans with impaired JNK1-dependent responses to IL-17A/F and TGF-beta. SCIENCE IMMUNOLOGY. WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE, 2019, roč. 4, č. 41, s. 1-13. ISSN 2470-9468. Dostupné z: https://dx.doi.org/10.1126/sciimmunol.aax7965. |
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@article{1637576,
author = {Li, J. and Ritelli, M. and Ma, C. S. and Rao, G. and Habib, T. and Corvilain, E. and Bougarn, S. and Cypowyj, S. and Grodecká, Lucie and Levy, R. and Beziat, V. and Shang, L. and Payne, K. and Avery, D. T. and Migaud, M. and Boucherit, S. and Boughorbel, S. and Guennoun, A. and Chrabieh, M. and Rapaport, F. and Bigio, B. and Itan, Y. and Boisson, B. and CormierandDaire, V. and Syx, D. and Malfait, F. and Zoppi, N. and Abel, L. and Freiberger, Tomáš and Dietz, H. C. and Marr, N. and Tangye, S. G. and Colombi, M. and Casanova, J. L. and Puel, A. and Fieschi, C.},
article_location = {WASHINGTON},
article_number = {41},
doi = {http://dx.doi.org/10.1126/sciimmunol.aax7965},
keywords = {GROWTH-FACTOR-BETA; EHLERS-DANLOS-SYNDROME; OF-FUNCTION MUTATIONS; NH2-TERMINAL KINASE (JNK)1; INBORN-ERRORS; EXTRACELLULAR-MATRIX; CELL-DIFFERENTIATION; AORTIC-ANEURYSMS; STAT1 MUTATIONS; MARFAN-SYNDROME},
language = {eng},
issn = {2470-9468},
journal = {SCIENCE IMMUNOLOGY},
title = {Chronic mucocutaneous candidiasis and connective tissue disorder in humans with impaired JNK1-dependent responses to IL-17A/F and TGF-beta},
url = {https://immunology.sciencemag.org/content/4/41/eaax7965},
volume = {4},
year = {2019}
}
TY - JOUR
ID - 1637576
AU - Li, J. - Ritelli, M. - Ma, C. S. - Rao, G. - Habib, T. - Corvilain, E. - Bougarn, S. - Cypowyj, S. - Grodecká, Lucie - Levy, R. - Beziat, V. - Shang, L. - Payne, K. - Avery, D. T. - Migaud, M. - Boucherit, S. - Boughorbel, S. - Guennoun, A. - Chrabieh, M. - Rapaport, F. - Bigio, B. - Itan, Y. - Boisson, B. - Cormier-Daire, V. - Syx, D. - Malfait, F. - Zoppi, N. - Abel, L. - Freiberger, Tomáš - Dietz, H. C. - Marr, N. - Tangye, S. G. - Colombi, M. - Casanova, J. L. - Puel, A. - Fieschi, C.
PY - 2019
TI - Chronic mucocutaneous candidiasis and connective tissue disorder in humans with impaired JNK1-dependent responses to IL-17A/F and TGF-beta
JF - SCIENCE IMMUNOLOGY
VL - 4
IS - 41
SP - 1-13
EP - 1-13
PB - AMER ASSOC ADVANCEMENT SCIENCE
SN - 24709468
KW - GROWTH-FACTOR-BETA
KW - EHLERS-DANLOS-SYNDROME
KW - OF-FUNCTION MUTATIONS
KW - NH2-TERMINAL KINASE (JNK)1
KW - INBORN-ERRORS
KW - EXTRACELLULAR-MATRIX
KW - CELL-DIFFERENTIATION
KW - AORTIC-ANEURYSMS
KW - STAT1 MUTATIONS
KW - MARFAN-SYNDROME
UR - https://immunology.sciencemag.org/content/4/41/eaax7965
L2 - https://immunology.sciencemag.org/content/4/41/eaax7965
N2 - Genetic etiologies of chronic mucocutaneous candidiasis (CMC) disrupt human IL-17A/F-dependent immunity at mucosal surfaces, whereas those of connective tissue disorders (CTDs) often impair the TGF-beta-dependent homeostasis of connective tissues. The signaling pathways involved are incompletely understood. We report a three-generation family with an autosomal dominant (AD) combination of CMC and a previously undescribed form of CTD that clinically overlaps with Ehlers-Danlos syndrome (EDS). The patients are heterozygous for a private splice-site variant of MAPK8, the gene encoding c-Jun N-terminal kinase 1 (JNK1), a component of the MAPK signaling pathway. This variant is loss-of-expression and loss-of-function in the patients' fibroblasts, which display AD JNK1 deficiency by haploinsufficiency. These cells have impaired, but not abolished, responses to IL-17A and IL-17F. Moreover, the development of the patients' TH17 cells was impaired ex vivo and in vitro, probably due to the involvement of JNK1 in the TGF-beta-responsive pathway and further accounting for the patients' CMC. Consistently, the patients' fibroblasts displayed impaired JNK1- and c-Jun/ATF-2-dependent induction of key extracellular matrix (ECM) components and regulators, but not of EDS-causing gene products, in response to TGF-beta. Furthermore, they displayed a transcriptional pattern in response to TGF-beta different from that of fibroblasts from patients with Loeys-Dietz syndrome caused by mutations of TGFBR2 or SMAD3, further accounting for the patients' complex and unusual CTD phenotype. This experiment of nature indicates that the integrity of the human JNK1-dependent MAPK signaling pathway is essential for IL-17A- and IL-17F-dependent mucocutaneous immunity to Candida and for the TGF-beta-dependent homeostasis of connective tissues.
ER -
LI, J., M. RITELLI, C. S. MA, G. RAO, T. HABIB, E. CORVILAIN, S. BOUGARN, S. CYPOWYJ, Lucie GRODECKÁ, R. LEVY, V. BEZIAT, L. SHANG, K. PAYNE, D. T. AVERY, M. MIGAUD, S. BOUCHERIT, S. BOUGHORBEL, A. GUENNOUN, M. CHRABIEH, F. RAPAPORT, B. BIGIO, Y. ITAN, B. BOISSON, V. CORMIER-DAIRE, D. SYX, F. MALFAIT, N. ZOPPI, L. ABEL, Tomáš FREIBERGER, H. C. DIETZ, N. MARR, S. G. TANGYE, M. COLOMBI, J. L. CASANOVA, A. PUEL a C. FIESCHI. Chronic mucocutaneous candidiasis and connective tissue disorder in humans with impaired JNK1-dependent responses to IL-17A/F and TGF-beta. \textit{SCIENCE IMMUNOLOGY}. WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE, 2019, roč.~4, č.~41, s.~1-13. ISSN~2470-9468. Dostupné z: https://dx.doi.org/10.1126/sciimmunol.aax7965.
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