Energy metabolism and autoimmune diseases -
A few years ago, research by teams led by Professor Dominik Müller at the Max Delbrück Center for Molecular Medicine and the Experimental and Clinical Research Center, a joint institution of Charité — Universitätsmedizin Berlin and Max Delbrück Center ECRC in Berlin, Germany and Professor Markus Kleinewietfeld at the VIB Center for Inflammation Research and Hasselt University in Belgium, as well as by colleagues of theirs, revealed that too much salt in our diet can negatively affect the metabolism and energy balance in certain types of innate immune cells called monocytes and macrophages and stop them from working properly.
They further showed that salt triggers malfunctions in the mitochondria, the power plants of our cells. Inspired by these findings, the research groups wondered whether excessive salt intake might also create a similar problem in adaptive immune cells like regulatory T cells. Regulatory T cells, also known as Tregs, are an essential part of the adaptive immune system.
They are responsible for maintaining the balance between normal function and unwanted excessive inflammation. Scientists believe that the deregulation of Tregs is linked to the development of autoimmune diseases like multiple sclerosis.
Recent research has identified problems in mitochondrial function of Tregs from patients with autoimmunity, yet the contributing factors remain elusive. Previous research has also shown that excess salt could impact Treg function by inducing an autoimmune-like phenotype. In other words, too much salt makes the Treg cells look like those involved in autoimmune conditions.
However, exactly how sodium impairs Treg function had not yet been uncovered. Salt disrupts the function of immune regulators Tregs : Their mitochondria temporarily produce less energy, thus altering cellular metabolism.
The new international study led by Kleinewietfeld and Müller and first-authored by Dr. Beatriz Côrte-Real and Dr. Ibrahim Hamad — both of whom work at the VIB Center for Inflammation Research and Hasselt University in Belgium — has now discovered that sodium disrupts Treg function by altering cellular metabolism through interference with mitochondrial energy generation.
This mitochondrial problem seems to be the initial step in how salt modifies Treg function, leading to changes in gene expression that showed similarities to those of dysfunctional Tregs in autoimmune conditions.
Even a short-term disruption of mitochondrial function had long-lasting consequences for the fitness and immune-regulating capacity of Tregs in various experimental models.
The new findings suggest that sodium may be a factor that could contribute to Treg dysfunction, potentially playing a role in different diseases, although this needs to be confirmed in further studies.
Beatriz Côrte-Real, Ibrahim Hamad et al. Dominik Müller Hypertension-Mediated End-Organ Damage Lab Max Delbrück Center and the Experimental and Clinical Research Center ECRC dominik.
mueller mdc-berlin. Markus Kleinewietfeld Kleinewietfeld Lab VIB Center for Inflammation Research and Hasselt University markus. kleinewietfeld uhasselt. schluetter mdc-berlin. de or presse mdc-berlin. Pharmacologic manipulation of membrane order by adding 7-ketocholesterol and cholesterol into the culture media, which has been shown to reduce lipid order, inhibits CD4 T-cell proliferation and IL-2 production.
Lipid metabolism is thus critically important in determining access to stored energy, but even more relevant by altering the composition of cellular membranes. Rheumatoid arthritis RA is a prototypic autoimmune disease, characterized by persistent immune activation [ 31 , 32 ].
The strongest genetic risk factors have been associated with the human leukocyte antigen region and with genes setting cytoplasmic signaling thresholds [ 33 ]. Pathogenic immune functions include excess cytokine production, dysregulated proliferation of synovial fibroblasts, formation of complex lymphoid microstructures in inflamed joints, autoantibody production, and uncontrolled activity of bone-destructive osteoclasts.
The prevailing concept has been that identifying the autoantigens, assumed to be the original trigger, would reveal the pathogenesis. Over the last decade, antigen-nonspecific abnormalities have been implicated in the dysregulated immune system of RA patients and the question arises of to what extent metabolic dysregulation contributes to the breakdown of self-tolerance.
Indeed, several glycolytic enzymes, including glucosephosphate isomerase, aldolase and enolase, have been identified as antigens recognized by autoantibodies [ 34 - 36 ].
This may reflect the propensity of RA patients to break self-tolerance against a wide variety of antigens. How autoantibodies to glycolytic enzymes would alter metabolic competence of immune cells is unclear. Proteomic analysis of synovial fluid has revealed that proteins involved in glycolytic pathways are highly expressed in RA patients, but not in synovial fluids from osteoarthritis patients, which is in accordance with upregulation of glycolytic flux in synovial lesions [ 37 ].
A recent study has examined the metabolic status of CD4 T cells in RA patients Figure 2 [ 38 ]. The analysis focused on naïve CD4 T cells, thus excluding T cells directly involved in the inflammatory process itself.
When stimulated through the T-cell receptor and transitioning into effector T cells, such naïve CD4 T cells are expected to swiftly upregulate aerobic glycolysis, following a classical Warburg effect. Remarkably, RA T cells failed to produce as much ATP and lactate as healthy control T cells, while vigorously proliferating [ 38 ].
PFKFB3 is a rate-limiting enzyme in the glycolytic pathway, making it an ideal target for regulatory interference. PFKFB3 is a bifunctional enzyme that prompts glycolytic flux by generating fructose-2,6-bisphosphate, an allosteric activator of the key glycolytic enzyme 6-phosphofructokinase.
PFKFB3 is considered to have a high ratio of kinase to phosphatase activity and converts fructose-2,6-bisphosphate to fructosephosphate when functioning as a phosphatase. The study employed a gene expression screen for 29 glycolysis-related markers, and PFKFB3 was the only marker that was significantly suppressed in RA T cells.
Metabolic reprogramming in rheumatoid arthritis T cells. The defect in glycolysis has consequences for the affected T cells Figure 2. Not only do RA T cells produce less ATP and lactate, they also shunt glucose towards the pentose phosphate pathway, and generate increased levels of nicotinamide adenine dinucleotide phosphate NADPH , the principal intracellular reductant [ 38 ].
NADPH converts glutathione disulfide to its reduced form glutathione, eventually diminishing intracellular reactive oxygen species ROS. ROS have traditionally attracted attention for their potential to directly harm proteins, lipids, DNA, cellular organelles and membranes.
Recently, ROS have been recognized as important regulators of intracellular signaling pathways. Previous studies have connected increasing risk for arthritic disease with NOX2 deficiency.
Also, reduced ROS production is associated with increased severity of joint inflammation [ 39 - 41 ]. This indicates a role for oxidative burst in protection from arthritis. Metabolic consequences of PFKFB3 deficiency in RA T cells are not limited to enhancing NADPH and pentose production.
PFKFB3 also represses the activity of autophagy, which is a catabolic process and is upregulated to degrade cytoplasmic contents under energy deprivation [ 42 ].
Considering their decreased glycolytic flux, RA T cells would be expected to resort to enhanced autophagic activity to fulfill their demands for energy and biosynthetic macromolecules. However, RA T cells are unable to upregulate autophagic flux and are forced into apoptosis in the presence of the autophagy inhibitor 3-methylamphetamine [ 38 ].
This insufficient autophagic activity in RA T cells can be, at least partially, repaired by overexpression of PFKFB3, which suggests an important role of PFKFB3 in the coordination of the autophagy machinery. Why RA T cells fail to induce PFKFB3 and essentially commit to an anti-Warburg effect is not understood.
However, this is not the first abnormality in the naïve CD4 T-cell pool of RA patients. Over the last decade, it has become obvious that T cells in RA patients are prematurely aged [ 43 - 46 ]. The accelerated aging phenotype of RA T cells includes shortening of telomeres, loss of CD28 and reduced efficiency of DNA repair mechanisms [ 46 - 49 ].
T-cell aging has been associated with resetting of signaling thresholds due to age-related changes in phosphatase activity [ 50 , 51 ].
It is currently unknown whether the metabolic reprogramming of RA T cells is mechanistically connected to the pre-senescent phenotype of the cells.
It is conceivable that the energy deficiency of the cells shortens their lifespan, thus imposing proliferative pressure that ages the T-cell compartment.
Alternatively, senescence-associated shifts in gene expression could affect production of glycolytic enzymes and thus result in altered glycolytic flux. Independent of whether glycolytic insufficiency precedes or follows the process of T-cell aging, lower ability to generate ATP should render T cells sensitive to apoptosis and thus cause lymphopenia-induced T-cell turnover.
Lymphopenic hosts are more likely to have autoreactive T cells, because homeostatic T-cell expansion relies on recognition of autoantigens [ 32 ]. The wide range of autoantibodies in systemic lupus erythematosus SLE has fostered concepts of intrinsic B-cell abnormalities in this autoimmune disease [ 52 ].
Convincing data have, however, revealed that T cells critically participate in the pathogenesis of SLE due to their capabilities to guide B cells in autoantibody production. Both abnormal T-cell activation and signaling are suspected to contribute to aberrant B-cell response. Efforts to understand how dysfunctional T cells promote disease processes in SLE have recently focused on cell-intrinsic abnormalities, including metabolic shifts in T cells from SLE patients.
In contrast to healthy lymphocytes, lupus T cells secure ATP production through OXPHOS, rather than upregulating aerobic glycolysis [ 53 ]. Glycolytic activity in chronically stimulated human T cells can be significantly lower than in acutely activated cells [ 53 ]. Underlying mechanisms are unknown, but it has been speculated that reduced CD28 expression may go hand in hand with less active aerobic glycolysis.
SLE T cells have elevated mitochondrial membrane potential, produce more ROS and have reduced intracellular glutathione [ 54 , 55 ], possibly caused by the acceleration of the TCA cycle resulting in excessive ROS generation due to the leakiness of the electron transport chain.
Convincing evidence has accumulated over the last decade that SLE is a disease associated with increased oxidative stress [ 56 ] and excessive oxidative capacity has been implicated in underlying immune dysfunction, autoantibody production and in the cardiovascular complications of the disease.
Evidence has been provided that dysfunctional mitochondria are the main source of excess ROS in SLE [ 57 ]. A study by Kato and Perl linked IL-4 and IL production in lupus T cells with increased activity of mTORC1 [ 58 ]. Excessive ROS production and increased mTORC1 activity have prompted clinical trials designed to correct these metabolic defects, ranging from inhibition of mTORC1 by rapamycin to reversal of glutathione depletion by N- acetylcysteine [ 59 , 60 ].
Spontaneous mTORC1 activity would suggest that AMPK is insufficiently activated in SLE T cells, which is unexpected under conditions of highly activated mitochondrial activity and ROS release.
A metabolomic analysis of SLE sera has revealed that energy biogenesis from all sources is diminished.
Based on a broad analysis of metabolites, glycolysis, fatty acid beta-oxidation and amino acid metabolism all appear to be dampened, while levels of free fatty acids are increased, supporting the notion that SLE is associated with abnormalities in lipid metabolism [ 61 ].
Diminished energy biosynthesis should activate AMPK and lead to subsequent downregulation of mTORC1. Further studies are urgently needed to integrate these findings and to connect them to the pathogenic role of lymphocytes in the disease.
In a recent study, McDonald and colleagues investigated the complex crosstalk between lipid metabolism and T-cell dysfunctions in lupus. Compared with healthy controls, CD4 T cells from SLE patients had significantly elevated lipid raft-associated glycosphingolipids [ 62 ] Figure 3.
Also, such T cells had elevated expression of Liver X receptor, a member of the nuclear receptor family of transcription factors that function as important regulators of cholesterol and fatty acid homeostasis.
Altered glycosphingolipids and cholesterol homeostasis in lipid rafts led to abnormal T-cell receptor signaling, most probably by promoting formation of raft structures and increasing lipid raft localization of critical signaling mediators, such as the protein tyrosine kinase LCK and CD Inhibition of glycosphingolipids metabolism normalized CD4 T-cell signaling and decreased anti-double-stranded DNA antibody production by autologous B cells.
These data support the notion that lipid biosynthesis is closely correlated with membrane function and setting the threshold for signaling. The molecular mechanisms that drive lipid metabolic dysfunction in T cells in SLE have not been clarified. Altered membrane lipids in lupus T cells.
The amount of glycerophospholipid, glycosphingolipids and cholesterol is tightly regulated and critical for T-cell receptor TCR signaling in healthy T cells. T cells from systemic lupus erythematosus patients exhibit excessive glycosphingolipid homeostasis, leading to aggregated lipid rafting and altered TCR signaling.
While not a rheumatic disease, studies on pathogenic pathways in the autoimmune disease multiple sclerosis have been highly informative in deciphering immune abnormalities that lead to immune-driven tissue damage.
In terms of metabolic abnormalities, elevated levels of both glutamine and glutamate have been reported in clinical cases of multiple sclerosis [ 63 ] and glutamate concentrations have been related to multiple sclerosis severity [ 64 ], raising the interesting question of whether the neurotransmitter glutamate could fuel tissue-injurious immunity.
Besides its role as a neurotransmitter, glutamate is a key source of energy in neurons, glia and immune cells. Lymphocytes possess glutamine synthetase activity, enabling them to synthesize glutamine from glutamate [ 65 ]. Following activation, T cells boost glutamine uptake by 5-fold to fold compared with the resting state.
Glutamine uptake depends on the transporter ASCT2, a molecule that has recently been implicated in affecting the development of CD4 Th1 and Th17 effector cells via regulating the activity of the kinase mammalian target of rapamycin [ 24 ].
Mice deficient for the amino acid transporter ASCT2 are refractory to the induction of experimental allergic encephalomyelitis, an animal model of multiple sclerosis [ 24 ]. In essence, T cells depend on transporter-supported glutamine import to nurture their activation and their pathogenic role in central nervous system inflammation.
Highly proliferative immune cells share with cancer cells the switch to progrowth glycolysis, which secures both ATP and macromolecules. Another key nutrient source is amino acids, particularly the nonessential amino acid glutamine, which provide energy as well as biosynthetic precursors for proteins, nucleic acids and lipids.
More needs to be learned about lipid metabolism on the cellular level, because lipids serve as densely-packed energy reservoirs and are essential building blocks for membranes and signaling molecules. A simple paradigm would assume that chronic autoimmune diseases, which depend on long-lived and highly-differentiated lymphocytes, are a high energy-consuming state susceptible to metabolic manipulations.
However, emerging data in RA and SLE attest to the complexity of metabolic programs in chronic autoimmunity. RA T cells have a defect in PFKFB3, a gatekeeper enzyme in the glycolytic pathway, leaving them energy deprived.
Conversely, lupus T cells appear metabolically more active, producing excess ROS. Signaling abnormalities in lupus T cells are associated with alterations in the lipid composition of cell membranes.
Differences in the redox status of RA and SLE patients, with oxidative pressure in SLE and reductive pressure in RA, suggest fundamentally distinct metabolic programs in both disease processes, which may reflect differences in how nutrients are handled in different microenvironments or may indicate differences regarding the metabolic niches to which lymphocytes are exposed.
Data from RA and SLE challenge the simplified model that surplus immune activation is equivalent to surplus nutrient supply and instead give rise to the concept that disease-specific patterning of metabolic abnormalities may exist. Disease-specific abnormalities have implications for diagnostic and therapeutic approaches, because a one-size-fits-all approach may not work.
However, modifying cell-internal metabolism in T cells represents a novel therapeutic opportunity to treat autoimmunity. This would indeed be good news for rheumatologists because it may pave the way to highly sophisticated disease-adapted immunomodulation instead of using broad-based, nonspecific immunosuppression.
Warburg O. On respiratory impairment in cancer cells. CAS PubMed Google Scholar. Hotamisligil GS. Inflammation and metabolic disorders. Article CAS PubMed Google Scholar. Warburg O, Gawehn K, Geissler AW. Metabolism of leukocytes. Z Naturforsch B.
Frauwirth KA, Riley JL, Harris MH, Parry RV, Rathmell JC, Plas DR, et al. The CD28 signaling pathway regulates glucose metabolism.
Sinclair LV, Rolf J, Emslie E, Shi YB, Taylor PM, Cantrell DA. Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation.
Nat Immunol. Article PubMed Central CAS PubMed Google Scholar. Bental M, Deutsch C. Metabolic changes in activated T cells: an NMR study of human peripheral blood lymphocytes.
Magn Reson Med. Kovacs B, Maus MV, Riley JL, Derimanov GS, Koretzky GA, June CH, et al. Proc Natl Acad Sci U S A. Shi LZ, Wang R, Huang G, Vogel P, Neale G, Green DR, et al.
HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med. Pearce EL, Walsh MC, Cejas PJ, Harms GM, Shen H, Wang LS, et al. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Gaber T, Schellmann S, Erekul KB, Fangradt M, Tykwinska K, Hahne M, et al.
J Immunol. Gaber T, Tran CL, Schellmann S, Hahne M, Strehl C, Hoff P, et al. Eur J Immunol. Goronzy JJ, Shao L, Weyand CM. Immune aging and rheumatoid arthritis. Rheum Dis Clin North Am. Article PubMed Central PubMed Google Scholar.
Caro-Maldonado A, Wang R, Nichols AG, Kuraoka M, Milasta S, Sun LD, et al. Metabolic reprogramming is required for antibody production that is suppressed in anergic but exaggerated in chronically BAFF-exposed B cells.
Greiner EF, Guppy M, Brand K. Glucose is essential for proliferation and the glycolytic enzyme induction that provokes a transition to glycolytic energy production. J Biol Chem. Wang R, Dillon CP, Shi LZ, Milasta S, Carter R, Finkelstein D, et al. The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation.
Macintyre AN, Gerriets VA, Nichols AG, Michalek RD, Rudolph MC, Deoliveira D, et al. The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function. Cell Metab. Dufort FJ, Gumina MR, Ta NL, Tao Y, Heyse SA, Scott DA, et al.
Glucose-dependent de novo lipogenesis in B lymphocytes: a requirement for ATP-citrate lyase in lipopolysaccharide-induced differentiation. Posttranscriptional control of T cell effector function by aerobic glycolysis.
van der Windt GJ, Everts B, Chang CH, Curtis JD, Freitas TC, Amiel E, et al. Delgoffe GM, Kole TP, Zheng Y, Zarek PE, Matthews KL, Xiao B, et al.
The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Araki K, Turner AP, Shaffer VO, Gangappa S, Keller SA, Bachmann MF, et al. mTOR regulates memory CD8 T-cell differentiation.
Carr EL, Kelman A, Wu GS, Gopaul R, Senkevitch E, Aghvanyan A, et al. Ardawi MS. Glutamine and glucose metabolism in human peripheral lymphocytes. Nakaya M, Xiao Y, Zhou X, Chang JH, Chang M, Cheng X, et al. Inflammatory T cell responses rely on amino acid transporter ASCT2 facilitation of glutamine uptake and mTORC1 kinase activation.
DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S, et al. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis.
Robichaud PP, Boulay K, Munganyiki JE, Surette ME. Fatty acid remodeling in cellular glycerophospholipids following the activation of human T cells. J Lipid Res. Bettens F, Kristensen F, Walker C, Bonnard GD, de Weck AL.
Lymphokine regulation of human lymphocyte proliferation: formation of resting G0 cells by removal of interleukin 2 in cultures of proliferating T lymphocytes. Cell Immunol. Lee J, Walsh MC, Hoehn KL, James DE, Wherry EJ, Choi Y. Regulator of fatty acid metabolism, acetyl coenzyme a carboxylase 1, controls T cell immunity.
Miguel L, Owen DM, Lim C, Liebig C, Evans J, Magee AI, et al. Goronzy JJ, Weyand CM. Developments in the scientific understanding of rheumatoid arthritis. Arthritis Res Ther. Weyand CM, Fujii H, Shao L, Goronzy JJ. Rejuvenating the immune system in rheumatoid arthritis.
Nat Rev Rheumatol. Jacob N, Jacob CO. Genetics of rheumatoid arthritis: an impressionist perspective. Article PubMed Google Scholar.
Schaller M, Burton DR, Ditzel HJ. Autoantibodies to GPI in rheumatoid arthritis: linkage between an animal model and human disease. Ukaji F, Kitajima I, Kubo T, Shimizu C, Nakajima T, Maruyama I. Ann Rheum Dis. Saulot V, Vittecoq O, Charlionet R, Fardellone P, Lange C, Marvin L, et al.
Presence of autoantibodies to the glycolytic enzyme alpha-enolase in sera from patients with early rheumatoid arthritis. Arthritis Rheum.
Balakrishnan L, Bhattacharjee M, Ahmad S, Nirujogi RS, Renuse S, Subbannayya Y, et al. Differential proteomic analysis of synovial fluid from rheumatoid arthritis and osteoarthritis patients.
Clin Proteomics. Yang Z, Fujii H, Mohan SV, Goronzy JJ, Weyand CM. Phosphofructokinase deficiency impairs ATP generation, autophagy, and redox balance in rheumatoid arthritis T cells.
Lee K, Won HY, Bae MA, Hong JH, Hwang ES. Gelderman KA, Hultqvist M, Olsson LM, Bauer K, Pizzolla A, Olofsson P, et al.
Rheumatoid arthritis: the role of reactive oxygen species in disease development and therapeutic strategies. Antioxid Redox Signal. Pizzolla A, Wing K, Holmdahl R. Am J Pathol.
Yang Z, Goronzy JJ, Weyand CM. Aging, autoimmunity and arthritis: T-cell senescence and contraction of T-cell repertoire diversity — catalysts of autoimmunity and chronic inflammation. Weyand CM, Fulbright JW, Goronzy JJ. Immunosenescence, autoimmunity, and rheumatoid arthritis.
Exp Gerontol. Goronzy JJ, Li G, Yang Z, Weyand CM. The janus head of T cell aging — autoimmunity and immunodeficiency. Front Immunol. Weyand CM, Yang Z, Goronzy JJ.
T-cell aging in rheumatoid arthritis. Curr Opin Rheumatol. Fujii H, Shao L, Colmegna I, Goronzy JJ, Weyand CM. Telomerase insufficiency in rheumatoid arthritis. Shao L, Fujii H, Colmegna I, Oishi H, Goronzy JJ, Weyand CM. Deficiency of the DNA repair enzyme ATM in rheumatoid arthritis.
Schmidt D, Goronzy JJ, Weyand CM. J Clin Invest. Li G, Yu M, Lee WW, Tsang M, Krishnan E, Weyand CM, et al. Decline in miRa expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity. Nat Med. Yu M, Li G, Lee WW, Yuan M, Cui D, Weyand CM, et al. Signal inhibition by the dual-specific phosphatase 4 impairs T cell-dependent B-cell responses with age.
Tsokos GC. Systemic lupus erythematosus. N Engl J Med. Wahl DR, Petersen B, Warner R, Richardson BC, Glick GD, Opipari AW. Characterization of the metabolic phenotype of chronically activated lymphocytes. Gergely Jr P, Grossman C, Niland B, Puskas F, Neupane H, Allam F, et al.
Mitochondrial hyperpolarization and ATP depletion in patients with systemic lupus erythematosus. Perl A. Oxidative stress in the pathology and treatment of systemic lupus erythematosus. Systems biology of lupus: mapping the impact of genomic and environmental factors on gene expression signatures, cellular signaling, metabolic pathways, hormonal and cytokine imbalance, and selecting targets for treatment.
Doherty E, Oaks Z, Perl A. Increased mitochondrial electron transport chain activity at complex I is regulated by N-acetylcysteine in lymphocytes of patients with systemic lupus erythematosus. Kato H, Perl A. Fernandez D, Bonilla E, Mirza N, Niland B, Perl A. Rapamycin reduces disease activity and normalizes T cell activation-induced calcium fluxing in patients with systemic lupus erythematosus.
Lai ZW, Hanczko R, Bonilla E, Caza TN, Clair B, Bartos A, et al. N-acetylcysteine reduces disease activity by blocking mammalian target of rapamycin in T cells from systemic lupus erythematosus patients: a randomized, double-blind, placebo-controlled trial.
Wu T, Xie C, Han J, Ye Y, Weiel J, Li Q, et al. Metabolic disturbances associated with systemic lupus erythematosus. PLoS One. McDonald G, Deepak S, Miguel L, Hall CJ, Isenberg DA, Magee AI, et al. Sarchielli P, Greco L, Floridi A, Gallai V.
A recent study published in Energy metabolism and autoimmune diseases Reports by researchers at the LIH and the Energj of Luxembourg explores the Factors affecting metabolism of T Energy metabolism and autoimmune diseases metagolism to interfere with diseasex function of autoreactive Th17 cells implicated in autoimmune diseases, revealing qnd insights into the autoimkune between cellular metabolism and epigenetic modifications. T cells are a type of white blood cell that plays a critical role in our immune system. They help to protect us from pathogens such as viruses, bacteria, as well as attacking cancer cells. For example, Th17 cells have been linked to diseases like multiple sclerosis, psoriasis, and inflammatory bowel disease. A recent study by researchers the LIH and the University of Luxembourg aimed to understand the molecular and metabolic regulation of autoreactive Th17 cells to interfere with their ability to cause disease-causing function. Energy metabolism maintains the activation of intracellular autiimmune intercellular signal transduction, and plays a crucial role in immune response. Enedgy environmental stimulation, diweases cells change autoimnune resting to activation and trigger metabolic diseased. The immune system cells exhibit different metabolic Energy metabolism and autoimmune diseases diseasws performing functions. The study of immune metabolism provides new insights into the function of immune cells, including how they differentiate, migrate and exert immune responses. Studies of immune cell energy metabolism are beginning to shed light on the metabolic mechanism of disease progression and reveal new ways to target inflammatory diseases such as autoimmune diseases, chronic viral infections, and cancer. Here, we discussed the relationship between immune cells and metabolism, and proposed the possibility of targeted metabolic process for disease treatment.
Dieser bemerkenswerte Gedanke fällt gerade übrigens
Ich denke, dass es der Irrtum ist. Ich kann beweisen.
ich beglückwünsche, welche nötige Wörter..., der ausgezeichnete Gedanke
Wacker, dieser prächtige Gedanke fällt gerade übrigens
Absolut ist mit Ihnen einverstanden. Ich denke, dass es die gute Idee ist.