Autocrine vitamin D signaling switches off pro-inflammatory programs of TH1 cells

被引:138
作者
Chauss, Daniel [1 ]
Freiwald, Tilo [1 ,2 ]
McGregor, Reuben [1 ,3 ]
Yan, Bingyu [4 ]
Wang, Luopin [5 ]
Nova-Lamperti, Estefania [6 ]
Kumar, Dhaneshwar [1 ,5 ]
Zhang, Zonghao [7 ]
Teague, Heather [8 ]
West, Erin E. [9 ]
Vannella, Kevin M. [10 ,11 ]
Ramos-Benitez, Marcos J. [10 ,11 ]
Bibby, Jack [9 ]
Kelly, Audrey [12 ]
Malik, Amna [13 ]
Freeman, Alexandra F. [14 ]
Schwartz, Daniella M. [15 ]
Portilla, Didier [1 ,16 ,17 ]
Chertow, Daniel S. [10 ,11 ]
John, Susan [12 ]
Lavender, Paul [12 ]
Kemper, Claudia [9 ,18 ]
Lombardi, Giovanna [12 ]
Mehta, Nehal N. [8 ]
Cooper, Nichola [13 ]
Lionakis, Michail S. [19 ]
Laurence, Arian [20 ]
Kazemian, Majid [4 ,5 ]
Afzali, Behdad [1 ]
机构
[1] NIDDK, Immunoregulat Sect, Kidney Dis Branch, NIH, Bethesda, MD 20892 USA
[2] Goethe Univ, Univ Hosp Frankfurt, Dept Nephrol, Med Clin 3, Frankfurt, Germany
[3] Univ Auckland, Sch Med Sci, Dept Mol Med & Pathol, Auckland, New Zealand
[4] Purdue Univ, Dept Biochem, W Lafayette, IN 47907 USA
[5] Purdue Univ, Dept Comp Sci, W Lafayette, IN 47907 USA
[6] Univ Concepcion, Fac Pharm, Dept Clin Biochem & Immunol, Mol & Translat Immunol Lab, Concepcion, Chile
[7] Purdue Univ, Dept Agr & Biol Engn, W Lafayette, IN 47907 USA
[8] NHLBI, Lab Inflammat & Cardiometab Dis, NIH, Bldg 10, Bethesda, MD 20892 USA
[9] NHLBI, Complement & Inflammat Res Sect, NIH, Bldg 10, Bethesda, MD 20892 USA
[10] NIAID, Lab Immunoregulat, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[11] NIH, Emerging Pathogens Sect, Crit Care Med Dept, Clin Ctr, Bldg 10, Bethesda, MD 20892 USA
[12] Kings Coll London, Fac Life Sci & Med, Sch Immunol & Microbial Sci, Peter Gorer Dept Immunobiol, London, England
[13] Imperial Coll London, Dept Med, London, England
[14] NIAID, Lab Clin Immunol & Microbiol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[15] NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[16] Univ Virginia, Div Nephrol, Charlottesville, VA USA
[17] Univ Virginia, Ctr Immun Inflammat & Regenerat Med, Charlottesville, VA USA
[18] Univ Lubeck, Inst Syst Inflammat Res, Lubeck, Germany
[19] NIAID, Fungal Pathogenesis Sect, Lab Clin Immunol & Microbiol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[20] Univ Oxford, Nuffield Dept Med, Oxford, England
基金
英国惠康基金;
关键词
CD4(+) T-CELLS; 1,25-DIHYDROXYVITAMIN D-3; COMPLEMENT ACTIVATION; SUPER-ENHANCERS; GENERATION; EXPRESSION; INTERLEUKIN-6; PSORIASIS; CYTOKINES; IMMUNITY;
D O I
10.1038/s41590-021-01080-3
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The molecular mechanisms governing orderly shutdown and retraction of CD4(+) type 1 helper T (T(H)1) cell responses remain poorly understood. Here we show that complement triggers contraction of T(H)1 responses by inducing intrinsic expression of the vitamin D (VitD) receptor and the VitD-activating enzyme CYP27B1, permitting T cells to both activate and respond to VitD. VitD then initiated the transition from pro-inflammatory interferon-gamma(+) T(H)1 cells to suppressive interleukin-10(+) cells. This process was primed by dynamic changes in the epigenetic landscape of CD4(+) T cells, generating super-enhancers and recruiting several transcription factors, notably c-JUN, STAT3 and BACH2, which together with VitD receptor shaped the transcriptional response to VitD. Accordingly, VitD did not induce interleukin-10 expression in cells with dysfunctional BACH2 or STAT3. Bronchoalveolar lavage fluid CD4(+) T cells of patients with COVID-19 were T(H)1-skewed and showed de-repression of genes downregulated by VitD, from either lack of substrate (VitD deficiency) and/or abnormal regulation of this system. During homeostasis T(H)1 cells activate a cell-intrinsic inflammatory shutdown program and shift to IL-10 production. Chauss et al. find that this T(H)1 homeostatic program is dependent on vitamin D signaling and is disrupted in severe COVID-19.
引用
收藏
页码:62 / +
页数:36
相关论文
共 74 条
[1]   BACH2 immunodeficiency illustrates an association between super-enhancers and haploinsufficiency [J].
Afzali, Behdad ;
Gronholm, Juha ;
Vandrovcova, Jana ;
O'Brien, Charlotte ;
Sun, Hong-Wei ;
Vanderleyden, Ine ;
Davis, Fred P. ;
Khoder, Ahmad ;
Zhang, Yu ;
Hegazy, Ahmed N. ;
Villarino, Alejandro V. ;
Palmer, Ira W. ;
Kaufman, Joshua ;
Watts, Norman R. ;
Kazemian, Majid ;
Kamenyeva, Olena ;
Keith, Julia ;
Sayed, Anwar ;
Kasperaviciute, Dalia ;
Mueller, Michael ;
Hughes, Jason D. ;
Fuss, Ivan J. ;
Sadiyah, Mohammed F. ;
Montgomery-Recht, Kim ;
McElwee, Joshua ;
Restifo, Nicholas P. ;
Strober, Warren ;
Linterman, Michelle A. ;
Wingfield, Paul T. ;
Uhlig, Holm H. ;
Roychoudhuri, Rahul ;
Aitman, Timothy J. ;
Kelleher, Peter ;
Lenardo, Michael J. ;
O'Shea, John J. ;
Cooper, Nichola ;
Laurence, Arian D. J. .
NATURE IMMUNOLOGY, 2017, 18 (07) :813-+
[2]   Low Serum 25-hydroxyvitamin D (Vitamin D) Level Is Associated With Susceptibility to COVID-19, Severity, and Mortality: A Systematic Review and Meta-Analysis [J].
Akbar, Mohammad Rizki ;
Wibowo, Arief ;
Pranata, Raymond ;
Setiabudiawan, Budi .
FRONTIERS IN NUTRITION, 2021, 8
[3]   Calcifediol Treatment and Hospital Mortality Due to COVID-19: A Cohort Study [J].
Alcala-Diaz, Juan F. ;
Limia-Perez, Laura ;
Gomez-Huelgas, Ricardo ;
Martin-Escalante, Maria D. ;
Cortes-Rodriguez, Begona ;
Zambrana-Garcia, Jose L. ;
Entrenas-Castillo, Marta ;
Perez-Caballero, Ana I. ;
Lopez-Carmona, Maria D. ;
Garcia-Alegria, Javier ;
Lozano Rodriguez-Mancheno, Aquiles ;
Arenas-de Larriva, Maria del Sol ;
Perez-Belmonte, Luis M. ;
Jungreis, Irwin ;
Bouillon, Roger ;
Quesada-Gomez, Jose Manual ;
Lopez-Miranda, Jose .
NUTRIENTS, 2021, 13 (06)
[4]   Pathophysiology, Clinical Presentation, and Treatment of Psoriasis A Review [J].
Armstrong, April W. ;
Read, Charlotte .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2020, 323 (19) :1945-1960
[5]   In vitro generation of interleukin 10-producing regulatory CD4+ T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)- and Th2-inducing cytokines [J].
Barrat, FJ ;
Cua, DJ ;
Boonstra, A ;
Richards, DF ;
Crain, C ;
Savelkoul, HF ;
de Waal-Malefyt, R ;
Coffman, RL ;
Hawrylowicz, CM ;
O'Garra, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 195 (05) :603-616
[6]   Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells [J].
Bettelli, E ;
Carrier, YJ ;
Gao, WD ;
Korn, T ;
Strom, TB ;
Oukka, M ;
Weiner, HL ;
Kuchroo, VK .
NATURE, 2006, 441 (7090) :235-238
[7]   HUMAN PROTOONCOGENE C-JUN ENCODES A DNA-BINDING PROTEIN WITH STRUCTURAL AND FUNCTIONAL-PROPERTIES OF TRANSCRIPTION FACTOR AP-1 [J].
BOHMANN, D ;
BOS, TJ ;
ADMON, A ;
NISHIMURA, T ;
VOGT, PK ;
TJIAN, R .
SCIENCE, 1987, 238 (4832) :1386-1392
[8]  
Break TJ, 2021, SCIENCE, V373, DOI 10.1126/science.abi8835
[9]   Complement regulator CD46 temporally regulates cytokine production by conventional and unconventional T cells [J].
Cardone, John ;
Le Friec, Gaelle ;
Vantourout, Pierre ;
Roberts, Andrew ;
Fuchs, Anja ;
Jackson, Ian ;
Suddason, Tesha ;
Lord, Graham ;
Atkinson, John P. ;
Cope, Andrew ;
Hayday, Adrian ;
Kemper, Claudia .
NATURE IMMUNOLOGY, 2010, 11 (09) :862-U123
[10]   Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis [J].
Carvelli, Julien ;
Demaria, Olivier ;
Vely, Frederic ;
Batista, Luciana ;
Benmansour, Nassima Chouaki ;
Fares, Joanna ;
Carpentier, Sabrina ;
Thibult, Marie-Laure ;
Morel, Ariane ;
Remark, Romain ;
Andre, Pascale ;
Represa, Agnes ;
Piperoglou, Christelle ;
Cordier, Pierre Yves ;
Le Dault, Erwan ;
Guervilly, Christophe ;
Simeone, Pierre ;
Gainnier, Marc ;
Morel, Yannis ;
Ebbo, Mikael ;
Schleinitz, Nicolas ;
Vivier, Eric .
NATURE, 2020, 588 (7836) :146-+