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  1. Article ; Online: NAD

    Iske, Jasper / El Fatimy, Rachid / Nian, Yeqi / Ghouzlani, Amina / Eskandari, Siawosh K / Cetina Biefer, Hector Rodriguez / Vasudevan, Anju / Elkhal, Abdallah

    eLife

    2024  Volume 12

    Abstract: Septic shock is characterized by an excessive inflammatory response depicted in a cytokine storm that results from invasive bacterial, fungi, protozoa, and viral infections. Non-canonical inflammasome activation is crucial in the development of septic ... ...

    Abstract Septic shock is characterized by an excessive inflammatory response depicted in a cytokine storm that results from invasive bacterial, fungi, protozoa, and viral infections. Non-canonical inflammasome activation is crucial in the development of septic shock promoting pyroptosis and proinflammatory cytokine production via caspase-11 and gasdermin D (GSDMD). Here, we show that NAD
    MeSH term(s) Animals ; Mice ; Cytokines ; Interleukin-10 ; Inflammasomes ; NAD ; Shock, Septic/prevention & control ; Macrophages
    Chemical Substances Cytokines ; Interleukin-10 (130068-27-8) ; Inflammasomes ; NAD (0U46U6E8UK)
    Language English
    Publishing date 2024-02-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.88686
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  2. Article ; Online: The Fetal-Maternal Immune Interface in Uterus Transplantation.

    Iske, Jasper / Elkhal, Abdallah / Tullius, Stefan G

    Trends in immunology

    2020  Volume 41, Issue 3, Page(s) 213–224

    Abstract: Uterus transplants (UTxs) have been performed worldwide. Overall frequencies have been low, but globally initiated UTx programs are expected to increase clinical implementation. The uterus constitutes a unique immunological environment with specific ... ...

    Abstract Uterus transplants (UTxs) have been performed worldwide. Overall frequencies have been low, but globally initiated UTx programs are expected to increase clinical implementation. The uterus constitutes a unique immunological environment with specific features of tissue renewal and a receptive endometrium. Decidual immune cells facilitate embryo implantation and placenta development. Although UTx adds to the complexity of immunity during pregnancy and transplantation, the procedure provides a unique clinical and experimental model. We posit that understanding the distinct immunological properties at the interface of the transplanted uterus, the fetus and maternal circulation might provide valuable novel insights while improving outcomes for UTx. Here, we discuss immunological challenges and opportunities of UTx affecting mother, pregnancy and healthy livebirths.
    MeSH term(s) Embryo Implantation ; Female ; Fetus/immunology ; Humans ; Organ Transplantation ; Pregnancy ; Uterus/immunology ; Uterus/transplantation
    Language English
    Publishing date 2020-02-28
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2036831-8
    ISSN 1471-4981 ; 1471-4906
    ISSN (online) 1471-4981
    ISSN 1471-4906
    DOI 10.1016/j.it.2020.01.006
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  3. Article ; Online: NAD+ the disregarded molecule in cardiac metabolism.

    Biefer, Hector Rodriguez Cetina / Elkhal, Abdallah / Cesarovic, Nikola / Emmert, Maximilian Y

    European heart journal

    2020  Volume 41, Issue 9, Page(s) 983–986

    MeSH term(s) Energy Metabolism ; Humans ; Mitochondria/metabolism ; NAD/metabolism
    Chemical Substances NAD (0U46U6E8UK)
    Language English
    Publishing date 2020-02-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 603098-1
    ISSN 1522-9645 ; 0195-668X
    ISSN (online) 1522-9645
    ISSN 0195-668X
    DOI 10.1093/eurheartj/ehaa044
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  4. Article: Aspects of Tryptophan and Nicotinamide Adenine Dinucleotide in Immunity: A New Twist in an Old Tale.

    Rodriguez Cetina Biefer, Hector / Vasudevan, Anju / Elkhal, Abdallah

    International journal of tryptophan research : IJTR

    2017  Volume 10, Page(s) 1178646917713491

    Abstract: Increasing evidence underscores the interesting ability of tryptophan to regulate immune responses. However, the exact mechanisms of tryptophan's immune regulation remain to be determined. Tryptophan catabolism via the kynurenine pathway is known to play ...

    Abstract Increasing evidence underscores the interesting ability of tryptophan to regulate immune responses. However, the exact mechanisms of tryptophan's immune regulation remain to be determined. Tryptophan catabolism via the kynurenine pathway is known to play an important role in tryptophan's involvement in immune responses. Interestingly, quinolinic acid, which is a neurotoxic catabolite of the kynurenine pathway, is the major pathway for the
    Language English
    Publishing date 2017-06-14
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2517435-6
    ISSN 1178-6469
    ISSN 1178-6469
    DOI 10.1177/1178646917713491
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  5. Article ; Online: Impact of Metabolism on Immune Responses.

    Elkhal, Abdallah / Rodriguez Cetina Biefer, Hector / de la Fuente, Miguel A

    Journal of immunology research

    2018  Volume 2018, Page(s) 5069316

    MeSH term(s) Animals ; Asthma/immunology ; Cellular Reprogramming ; Dendritic Cells/immunology ; Estrogens/metabolism ; Humans ; Immune System/metabolism ; Immunity ; Lipid Metabolism ; Obesity/immunology ; Th1 Cells/immunology ; Toll-Like Receptors/metabolism
    Chemical Substances Estrogens ; Toll-Like Receptors
    Language English
    Publishing date 2018-07-26
    Publishing country Egypt
    Document type Editorial ; Introductory Journal Article
    ZDB-ID 2817541-4
    ISSN 2314-7156 ; 2314-8861
    ISSN (online) 2314-7156
    ISSN 2314-8861
    DOI 10.1155/2018/5069316
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  6. Article ; Online: Targeting age-specific changes in CD4

    Nian, Yeqi / Iske, Jasper / Maenosono, Ryoichi / Minami, Koichiro / Heinbokel, Timm / Quante, Markus / Liu, Yang / Azuma, Haruhito / Yang, Jinrui / Abdi, Reza / Zhou, Hao / Elkhal, Abdallah / Tullius, Stefan G

    Aging cell

    2021  Volume 20, Issue 2, Page(s) e13299

    Abstract: Age impacts alloimmunity. Effects of aging on T-cell metabolism and the potential to interfere with immunosuppressants have not been explored yet. Here, we dissected metabolic pathways of ... ...

    Abstract Age impacts alloimmunity. Effects of aging on T-cell metabolism and the potential to interfere with immunosuppressants have not been explored yet. Here, we dissected metabolic pathways of CD4
    MeSH term(s) Age Factors ; Animals ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; Graft Survival/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA
    Language English
    Publishing date 2021-01-26
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2113083-8
    ISSN 1474-9726 ; 1474-9718
    ISSN (online) 1474-9726
    ISSN 1474-9718
    DOI 10.1111/acel.13299
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  7. Article ; Online: Transplanting old organs promotes senescence in young recipients.

    Iske, Jasper / Roesel, Maximilian J / Martin, Friederike / Schroeter, Andreas / Matsunaga, Tomohisa / Maenosono, Ryoichi / Tripathi, Utkarsh / Xiao, Yao / Nian, Yeqi / Caldarone, Barbara J / Vondran, Florian W R / Sage, Peter T / Azuma, Haruhito / Abdi, Reza / Elkhal, Abdallah / Pirtskhalava, Tamar / Tchkonia, Tamara / Kirkland, James L / Zhou, Hao /
    Tullius, Stefan G

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

    2023  Volume 24, Issue 3, Page(s) 391–405

    Abstract: In clinical organ transplantation, donor and recipient ages may differ substantially. Old donor organs accumulate senescent cells that have the capacity to induce senescence in naïve cells. We hypothesized that the engraftment of old organs may induce ... ...

    Abstract In clinical organ transplantation, donor and recipient ages may differ substantially. Old donor organs accumulate senescent cells that have the capacity to induce senescence in naïve cells. We hypothesized that the engraftment of old organs may induce senescence in younger recipients, promoting age-related pathologies. When performing isogeneic cardiac transplants between age-mismatched C57BL/6 old donor (18 months) mice and young and middle-aged C57BL/6 (3- or 12- month-old) recipients , we observed augmented frequencies of senescent cells in draining lymph nodes, adipose tissue, livers, and hindlimb muscles 30 days after transplantation. These observations went along with compromised physical performance and impaired spatial learning and memory abilities. Systemic levels of the senescence-associated secretory phenotype factors, including mitochondrial DNA (mt-DNA), were elevated in recipients. Of mechanistic relevance, injections of mt-DNA phenocopied effects of age-mismatched organ transplantation on accelerating aging. Single treatment of old donor animals with senolytics prior to transplantation attenuated mt-DNA release and improved physical capacities in young recipients. Collectively, we show that transplanting older organs induces senescence in transplant recipients, resulting in compromised physical and cognitive capacities. Depleting senescent cells with senolytics, in turn, represents a promising approach to improve outcomes of older organs.
    MeSH term(s) Animals ; Mice ; Cellular Senescence ; Senotherapeutics ; Mice, Inbred C57BL ; Organ Transplantation/adverse effects ; DNA/pharmacology ; Aging/physiology
    Chemical Substances Senotherapeutics ; DNA (9007-49-2)
    Language English
    Publishing date 2023-10-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2060594-8
    ISSN 1600-6143 ; 1600-6135
    ISSN (online) 1600-6143
    ISSN 1600-6135
    DOI 10.1016/j.ajt.2023.10.013
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  8. Article ; Online: Taurodeoxycholic acid and valine reverse obesity-associated augmented alloimmune responses and prolong allograft survival.

    Quante, Markus / Iske, Jasper / Uehara, Hirofumi / Minami, Koichiro / Nian, Yeqi / Maenosono, Ryochi / Matsunaga, Tomohisa / Liu, Yang / Azuma, Haruhito / Perkins, David / Alegre, Maria-Luisa / Zhou, Hao / Elkhal, Abdallah / Tullius, Stefan G

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

    2021  Volume 22, Issue 2, Page(s) 402–413

    Abstract: Obesity initiates a chronic inflammatory network linked to perioperative complications and increased acute rejection rates in organ transplantation. Bariatric surgery is the most effective treatment of obesity recommended for morbidly obese transplant ... ...

    Abstract Obesity initiates a chronic inflammatory network linked to perioperative complications and increased acute rejection rates in organ transplantation. Bariatric surgery is the most effective treatment of obesity recommended for morbidly obese transplant recipients. Here, we delineated the effects of obesity and bariatric surgery on alloimmunity and transplant outcomes in diet-induced obese (DIO) mice. Allograft survival was significantly shorter in DIO-mice. When performing sleeve gastrectomies (SGx) prior to transplantation, we found attenuated T cell-derived alloimmune responses resulting in prolonged allograft survival. Administering taurodeoxycholic acid (TDCA) and valine, metabolites depleted in DIO-mice and restored through SGx, prolonged graft survival in DIO-mice comparable with SGx an dampened Th1 and Th17 alloimmune responses while Treg frequencies and CD4
    MeSH term(s) Allografts ; Animals ; Graft Rejection/etiology ; Graft Survival ; Heart Transplantation/adverse effects ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Obesity, Morbid ; Taurodeoxycholic Acid ; Valine
    Chemical Substances Taurodeoxycholic Acid (516-50-7) ; Valine (HG18B9YRS7)
    Language English
    Publishing date 2021-10-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2060594-8
    ISSN 1600-6143 ; 1600-6135
    ISSN (online) 1600-6143
    ISSN 1600-6135
    DOI 10.1111/ajt.16856
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  9. Article ; Online: Recipient sex and estradiol levels affect transplant outcomes in an age-specific fashion.

    Maenosono, Ryoichi / Nian, Yeqi / Iske, Jasper / Liu, Yang / Minami, Koichiro / Rommel, Tabea / Martin, Friederike / Abdi, Reza / Azuma, Haruhito / Rosner, Bernhard A / Zhou, Hao / Milford, Edgar / Elkhal, Abdallah / Tullius, Stefan G

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

    2021  Volume 21, Issue 10, Page(s) 3239–3255

    Abstract: Sex-specific influences have been shown for a variety of diseases. Whether donor or recipient sex and sex hormone levels impact alloimmune responses remains unclear. In unifactorial and multifactorial analyses of more than 400 000 SRTR listed kidney ... ...

    Abstract Sex-specific influences have been shown for a variety of diseases. Whether donor or recipient sex and sex hormone levels impact alloimmune responses remains unclear. In unifactorial and multifactorial analyses of more than 400 000 SRTR listed kidney transplant patients, we found that younger female recipients had an inferior death-censored graft survival that was independent of donor sex. In contrast, graft survival was superior in older female recipients, suggesting the impact of recipient sex hormones over chromosomal sex mismatches. Those clinical changes were delineated in experimental skin and heart transplant models showing a prolongation of graft survival in ovariectomized young female recipients. In contrast, graft survival was comparable in ovariectomized and naïve old female recipients. Young ovariectomized mice showed reduced amounts and a compromised T cell proliferation. Deprivation of female hormones dampened the production of interferon (IFN)-γ and interleukin (IL)-17
    MeSH term(s) Age Factors ; Aged ; Animals ; Estradiol ; Female ; Graft Rejection/etiology ; Graft Survival ; Humans ; Kidney Transplantation/adverse effects ; Male ; Mice ; Tissue Donors
    Chemical Substances Estradiol (4TI98Z838E)
    Language English
    Publishing date 2021-06-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2060594-8
    ISSN 1600-6143 ; 1600-6135
    ISSN (online) 1600-6143
    ISSN 1600-6135
    DOI 10.1111/ajt.16611
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  10. Article ; Online: T Cells Going Innate.

    Seyda, Midas / Elkhal, Abdallah / Quante, Markus / Falk, Christine S / Tullius, Stefan G

    Trends in immunology

    2016  Volume 37, Issue 8, Page(s) 546–556

    Abstract: Natural killer (NK) cell receptors (NKRs) play a crucial role in the homeostasis of antigen-experienced T cells. Indeed, prolonged antigen stimulation may induce changes in the receptor repertoire of T cells to a profile that features NKRs. Chronic ... ...

    Abstract Natural killer (NK) cell receptors (NKRs) play a crucial role in the homeostasis of antigen-experienced T cells. Indeed, prolonged antigen stimulation may induce changes in the receptor repertoire of T cells to a profile that features NKRs. Chronic antigen exposure, at the same time, has been shown to trigger the loss of costimulatory CD28 molecules with recently reported intensified antigen thresholds of antigen-experienced CD8(+) T cells. In transplantation, NKRs have been shown to assist allograft rejection in a CD28-independent fashion. We discuss here a role for CD28-negative T cells that have acquired the competency of the NKR machinery, potentially promoting allorecognition either through T cell receptor (TCR) crossreactivity or independently from TCR recognition. Collectively, NKRs can bring about innate-like T cells by providing alternative costimulatory pathways that gain relevance in chronic inflammation, potentially leading to resistance to CD28-targeting immunosuppressants.
    MeSH term(s) Adaptive Immunity ; Aging/genetics ; Aging/immunology ; Aging/metabolism ; Animals ; Antigens/immunology ; CD28 Antigens/metabolism ; Gene Expression Regulation ; Humans ; Immunity, Innate ; Immunosuppression ; Inflammation/genetics ; Inflammation/immunology ; Inflammation/metabolism ; Killer Cells, Natural/immunology ; Killer Cells, Natural/metabolism ; Lymphocyte Activation/genetics ; Lymphocyte Activation/immunology ; Receptors, Antigen, T-Cell ; Receptors, Natural Killer Cell/genetics ; Receptors, Natural Killer Cell/metabolism ; Signal Transduction ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism
    Chemical Substances Antigens ; CD28 Antigens ; Receptors, Antigen, T-Cell ; Receptors, Natural Killer Cell
    Language English
    Publishing date 2016-08
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2036831-8
    ISSN 1471-4981 ; 1471-4906
    ISSN (online) 1471-4981
    ISSN 1471-4906
    DOI 10.1016/j.it.2016.06.004
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