Hvorfor indgår TRPA1 receptoren i så mange sammenhænge – og indgår den i ME?

Jeg har i tidligere blogposts angivet receptoren TRPA1, som en mulig indgående (dysreguleret) faktor i både POTS, MCS, smerter mm. Nu er TRPA1 bare en lille brik i et større biokemisk puslespil, hvor mange andre faktorer indgår. For at forstå hvordan en enkelt receptor kan være så mangfoldig, er man nødt til at forstå, hvad der påvirker den. Førend TRPA1 bliver aktiveret, kan der være indtruffet en række af biokemiske reaktioner.

Lad os kigge på et eksempel på, hvordan fornemmelsen af kløe opstår rent biokemisk. Her er TRPA1 også involveret. Så hvilken kæde af reaktioner fører til, at TRPA1 receptoren aktiveres og giver et signal?

I artiklen The Epithelial Cell-Derived Atopic Dermatitis Cytokine TSLP Activates Neurons to Induce Itch findes en figur, der viser den biokemiske række af hændelser før TRPA1 aktiveres og sender besked op gennem rygraden til hjernen. (Klik ind og se figuren)

Som det fremgår af figuren er den en række af hændelser: PAR2 → ORAI1 → NFAT → TSLP → TSLP receptor → TRPA1.

Det er ikke af betydning i denne sammenhæng at forstå kæden af hændelser, men blot at forstå, at der ER en kæde af reaktioner.

Et andet eksempel er TRPA1s medvirken til smerte hypersensitivtet.

Klik ind på denne figur Model Depicting Functional Interactions between Bradykinin Receptors, TRPA1 and TRPV1.

Her ses rækken af biokemiske reaktioner (interaktioner) : Bradykinin receptoren påvirker TRPV1 receptoren, som igen påvirker TRPA1 receptoren.

Nu er det, at man skal tænke videre. Hvis TRPA1 også er involveret i ME, så kan TRPA1 måske i sig være dysreguleret eller den kan interagere med en receptor, der er dysreguleret.

Her er det værd at bemærke, at TRP receptorer ofte interagerer med receptorer, der kaldes G protein koblede receptorer

og

G protein koblede receptorer er ofte mål for autoimmune angreb.

Her kunne man måske tænke sig, at HVIS ME havde en autoimmun ætiologi, og HVIS dette var rettet mod en G protein koblet receptor, så kunne det MÅSKE forstyrre TRPA1.

Det kan naturligvis også være en hel anden mekanisme, - måske en mekansime, hvor der bliver ophobet en metabolit, som forstyrrer TRPA1.

TRPA1 and pain

An exciting new study about TRPA1 and pain:

Differential methylation of the TRPA1 promoter in pain sensitivity

References in relation to the paper:

Pain sensitivity may be influenced by lifestyle and environment

Derfor oplever enæggede tvillinger smerte forskelligt

Derfor føler eneggede tvillinger smerte forskjellig


..og lidt mere om TRPA1:

URMENNESKER GRÆD OGSÅ NÅR DE SKAR LØG

A role for TRPs in ME/CFS/POTS/MCS/pain/endothelial dysfunction...?

TRP blogposts - an overview

Exercise followed by pain and exhaustion - is it ME?

Exercise, fasting and cold temperatures as triggers for pain episodes followed by exhaustion and deep sleep. The period of pain is accompanied by breathing difficulties, tachycardia and sweating. Is it Myalgic encephalomyelitis?

No, it is Gain-of-Function Mutation in TRPA1.

A point mutation in the S4 transmembrane segment of TRPA1, a key sensor for environmental
irritants, causes Familial Episodic Pain Syndrome. The mutant channel showed a normal pharmacological profile but altered biophysical properties, with a 5-fold increase in inward current on activation at normal resting potentials.

Check out the fine paper and video that explains the discovery:

A Gain-of-Function Mutation in TRPA1 Causes Familial Episodic Pain Syndrome

More about TRPA1:

A role for TRPs in ME/CFS/POTS/MCS/pain/endothelial dysfunction...?

TRP blogposts - an overview

TRP blogposts - an overview

A role for TRPs in ME/CFS/POTS/MCS/pain/endothelial dysfunction...?

TRPA1, LPS and the possible connection to ME symptoms

TRPA1 and migraine - ME and migraine

Excessive activation of TRPA1 and TRPV1 by ROS may induce central sensitization – does it concern ME? 

TRPA1 og Multiple Chemical Sensitivity

A small peculiarity - ME, "ciguatoxin-look-alike" and TRPA1

Caveolae, eNOS and TRPA1?

Once again: TRPA1! Is activation of TRPA1 involved in ME?

Kan mRNA for TRPA1 benyttes som biomarkør for MCS?

Puslespilsbrikkerne: LPS, TLR4, TRPA1 og ME!?!

Vedvarende aktivering af TRPA1 og aflastning?

Variation i sensoriske reaktioner, TRP og stress

TRPA1, muskelaktivitet og påvirkning af det autonome nervesystem

ME, slow gastric emptying, serotonin and TRPA1

TRPA1, Hypoxia and ME?

Mitochondrial dysfunction - influence on TRPA1

Exercise and...TRPA1 and TRPV1

ME, neuropathy, TRPA1

TRPA1 involvement in autonomic dysfunction in ME?

TRPA1/TRPV4/PAR in inflammation/pain

Transient Receptor Potential in Multiple Chemical Sensitivity

TRP Ion Channels

A role for TRPs in ME/CFS/POTS/MCS/pain/endothelial dysfunction...?

TRPs are part of the biochemistry in health and disease.

A role for TRPs in ME/CFS/POTS/MCS/pain/endothelial dysfunction... ? Can some of the symptoms be explained, if we understand the TRPs?

TRP Ion Channels – especially TRPA1 references:

Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) [1]

Postural Orthostatic Tachycardia Syndrome (POTS) and vascular function [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9], [10], [11]

Multiple Chemical Sensitivity (MCS), asthma and airways [12] , [13] , [14] , [15] , [16] , [17], [18] , [19] , [20] , [21], [22] , [23]

Irritable Bowel Syndrome (IBS) and gastrointestinal tract [24], [25] , [26] , [27] , [28] , [29] , [30] , [31], [32] , [33]

Reflux [34] , [35]

Pain – inflammation – central sensitization - neuropathy [36], [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46], [47] , [48] , [49] , [50], [51], [52], [53] , [54] , [55], [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64], [65]

LPS – bacterial endotoxin [66]

Endothelial function/dysfunction [67], [68] , [69] , [70] , [71] ,[72] , [73]

Vascular function [74] , [75] , [76] , [77] , [78] , [79] ,[80] , [81] , [82]

Regulation af cerebral blood flow [83] ,[84] , [85]

Migraine [86], [87] , [88] , [89] , [90]

Exercise [91] , [92] , [93] , [94] , [95]

Stress [96] , [97] , [98]

Hypoxia, sensors of oxygen [99] , [100] , [101] , [102] , [103] ,[104]

Mitochondria, redox, ROS, RNS [105] , [106] , [107] , [108], [109] , [110] , [111]

Glial cells[112]

Dorsal root ganglion [113] , [114]

Vagus nerve [115]

Spinal Cord Injury (SCI) [116]

Bladder pain syndrome/ bladder dysfunction [117], [118], [119] , [120] , [121] , [122] , [123]

Rosacea [124]

Analgesia [125], [126], [127] , [128] , [129] , [130]

TRP in disease [131], [132]

TRP in sensory transduction and cellular signaling [133], [134] , [135]

TRP projects [136] , [137] ,

TRP patent applications [138] , [139] , [140], [141] , [142]

Treatment [143] , [144]

Inhibition of TRPA1 [145]

References:

[1] Translation from Mouse Sensory Neurons to Fibromyalgia and Chronic Fatigue Syndromes.

[2] Evidence for the pathophysiological relevance of TRPA1 receptors in the cardiovascular system in vivo

[3] TRPA1 channels in the vasculature

[4] Transient receptor potential channels and vascular function

[5] Transient receptor potential (TRP) channels, vascular tone and autoregulation of cerebral blood flow

[6] Endothelium-dependent cerebral artery dilation mediated by TRPA1 and Ca2+-Activated K+ channels

[7] TRPA1 receptors mediate environmental irritant-induced meningeal vasodilatation

[8] TRPA1 is involved in mediating vasodilation. TRPA1 can also influence changes in blood pressure of possible relevance to autonomic system reflexes and potentially to vasovagal/neurocardiogenic syncope disorders

[9] Involvement of TRPA1 receptors in meningeal blood flow induced by formation of nitroxyl (NO-/HNO)

[10] Redox Regulation of Endothelial Canonical Transient Receptor Potential Channels

[11] TRPA1 channels play a critical role in cold-induced vasodilatation

[12] Breathtaking TRP Channels: TRPA1 and TRPV1 in Airway Chemosensation and Reflex Control

[13] Activation of Transient Receptor Potential Ankyrin-1 (TRPA1) in Lung Cells by Wood Smoke Particulate Material

[14] Pre-clinical studies in cough research: Role of Transient Receptor Potential (TRP) channels

[15] Epithelial Cell TRPV1-Mediated Airway Sensitivity as a Mechanism for Respiratory Symptoms Associated with Gulf War Illness

[16] Transient Receptor Potential Channels Encode Volatile Chemicals Sensed by Rat Trigeminal Ganglion Neurons

[17] TRPA1 detects environmental chemicals and induces avoidance behavior and arousal from sleep

[18] Crucial Role of Transient Receptor Potential Ankyrin 1 and Mast Cells in Induction of Nonallergic Airway Hyperreactivity in Mice

[19] Transient receptor potential channels and occupational exposure

[20] Functional expression of the transient receptor potential channel TRPA1, a sensor for toxic lung inhalants, in pulmonary epithelial cells

[21] Pre-clinical studies in cough research: role of Transient Receptor Potential (TRP) channels

[22] A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma

[23] Multiple types of sensory neurons respond to irritating volatile organic compounds (VOCs): calcium fluorimetry of trigeminal ganglion neurons

[24] Increased capsaicin receptor TRPV1-expressing sensory fibres in irritable bowel syndrome and their correlation with abdominal pain

[25] Increased capsaicin receptor TRPV1-expressing sensory fibres in irritable bowel syndrome and their correlation with abdominal pain.

[26] QGP-1 cells release 5-HT via TRPA1 activation; a model of human enterochromaffin cells

[27] TRPA1 agonists delay gastric emptying in rats through serotonergic pathways

[28] TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells

[29] Psychological Co-morbidity in Functional Gastrointestinal Disorders: Epidemiology, Mechanisms and Management

[30] Sensory neuro-immune interactions differ between irritable bowel syndrome subtypes

[31] Acute Uterine Irritation Provokes Colonic Motility via Transient Receptor Potential A1-dependent Spinal NR2B Phosphorylation in Rats

[32] Identification of enteroendocrine cells that express TRPA1 channels in the mouse intestine

[33] Effects of novel TRPA1 receptor agonist ASP7663 in models of drug-induced constipation and visceral pain

[34] Airway Reflux, Cough and Respiratory Disease

[35] Inflammation and Oxidative Stress in Gastroesophageal Reflux Disease

[36] Two to tango: GPCR oligomers and GPCR-TRP channel interactions in nociception.

[37] Role of Oxidative Stress and Ca(2+) Signaling on Molecular Pathways of Neuropathic Pain in Diabetes: Focus on TRP Channels.

[38] TRPA1 Mediates Mechanical Sensitization in Nociceptors during Inflammation

[39] Breathtaking TRP Channels: TRPA1 and TRPV1 in Airway Chemosensation and Reflex Control

[40] Protease-activated Receptor-2 (PAR2) and Transient Receptor Potential Vanilloid 4 (TRPV4) Coupling is Required for Sustained Inflammatory Signaling

[41] Chemokines as Pain Mediators and Modulators

[42] Inhibiting TRPA1 ion channel reduces loss of cutaneous nerve fiber function in diabetic animals: sustained activation of the TRPA1 channel contributes to the pathogenesis of peripheral diabetic neuropathy

[43] The dynamic TRPA1 channel: a suitable pharmacological pain target?

[44] Sustained TRPA1 activation in vivo

[45] Reactive oxygen species enhance excitatory synaptic transmission in rat spinal dorsal horn neurons by activating TRPA1 and TRPV1 channels

[46] TRPA1: A Transducer and Amplifier of Pain and Inflammation

[47] Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling

[48] Reactive oxygen species enhance excitatory synaptic transmission in rat spinal dorsal horn neurons by activating TRPA1 and TRPV1 channels

[49] Acrolein involvement in sensory and behavioral hypersensitivity following spinal cord injury in the rat

[50] Hydrogen sulfide-induced mechanical hyperalgesia and allodynia require activation of both Cav3.2 and TRPA1 channels in mice

[51] Sustained firing of TRPA1 elicited by reactive agonists

[52] Transient receptor potential A1 increase glutamate release on brain stem neurons

[53] TRPV1 and TRPA1 Mediate Peripheral Nitric Oxide-Induced Nociception in Mice

[54] Spinal 12-lipoxygenase-derived hepoxilin A3 contributes to inflammatory hyperalgesia via activation of TRPV1 and TRPA1 receptors

[55] Sustained firing of TRPA1 elicited by reactive agonists

[56] Behavioral and Electrophysiological Study of Thermal and Mechanical Pain Modulation by TRP Channel Agonists

[57] Cortical spreading depression induces oxidative stress in the trigeminal nociceptive system

[58] Hypoxia-inducible Factor-1α (HIF1α) Switches on Transient Receptor Potential Ankyrin Repeat 1 (TRPA1) Gene Expression via a Hypoxia Response Element-like Motif to Modulate Cytokine Release

[59] Dynamic changes in the TRPA1 selectivity filter lead to progressive but reversible pore dilation

[60] NGF up-regulates TRPA1: implications for orofacial pain

[61] Differential methylation of the TRPA1 promoter in pain sensitivity

[62] Neurotrophins, endocannabinoids and thermo-transient receptor potential: a threesome in pain signalling

[63] Modulation of Transient Receptor Vanilloid 1 Activity by Transient Receptor Potential

Ankyrin 1

[64] TRP-channels as key integrators of lipid pathways in nociceptive neurons

[65] Methylglyoxal Evokes Pain by Stimulating TRPA1

[66] TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins

[67] TRP channels in endothelial function and dysfunction

[68] Expression and modulation of TRP channels in human microvascular endothelial cells

[69] Regulation and Function of TRPM7 in Human Endothelial Cells: TRPM7 as a Potential Novel Regulator of Endothelial Function

[70] Endothelium-dependent cerebral artery dilation mediated by transient receptor potential and Ca2+-activated K+ channels

[71] TRP channel Ca2+ sparklets: fundamental signals underlying endothelium-dependent hyperpolarization

[72] Model for TRPC5-mediated feedback of Ca2+ and NO signaling in endothelial cells and attenuation of Ca2+ entry through TRPC6 by NO in smooth muscle cells

[73] Cooperative Interaction of trp Melastatin Channel Transient Receptor Potential (TRPM2) With Its Splice Variant TRPM2 Short Variant Is Essential for Endothelial Cell Apoptosis

[74] Transient receptor potential channels and vascular function

[75] TRPA1 channels in the vasculature

[76] TRPV channels and vascular function

[77] TRP channels in vascular endothelial cells

[78] Evidence for the pathophysiological relevance of TRPA1 receptors in the cardiovascular system in vivo

[79] TRP channel and cardiovascular disease

[80] Transient Receptor Potential Channels in Cardiovascular Function and Disease

[81] Emerging concepts for the role of TRP channels in the cardiovascular system

[82] The NO/ONOO-cycle as the central cause of heart failure

[83] Endogenously-Generated Lipid Peroxidation Products Dilate Rat Cerebral Arteries by Activating TRPA1 Channels in the Endothelium

[84] TRANSIENT RECEPTOR POTENTIAL (TRP) CHANNELS, VASCULARTONE AND AUTOREGULATION OF CEREBRAL BLOOD FLOW

[85] Proposed Signaling Pathway for TRPA1-Mediated Vasodilation of Cerebral Arteries

[86] TRPA1 and other TRP channels in migraine

[87] Activation of TRPA1 on dural afferents: a potential mechanism of headache pain

[88] Parthenolide inhibits nociception and neurogenic vasodilatation in the trigeminovascular system by targeting the TRPA1 channel

[89] Cortical spreading depression induces oxidative stress in the trigeminal nociceptive system

[90] The TRPA1 Channel in Migraine Mechanism and Treatment

[91] Transient receptor potentials (TRPs) and anaphylaxis

[92] Muscle Afferent Receptors Engaged in Augmented Sympathetic Responsiveness in Peripheral Artery Disease

[93] Transient receptor potential A1 channel contributes to activation of the muscle reflex

[94] Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects

[95] Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with chronic fatigue syndrome, patients with multiple sclerosis, and healthy controls

[96] TRPV1 is a stress response protein in the central nervous system.

[97] Importance of TRP channels in pain: implications for stress

[98] Table 1. Cross-talk between several stress-related factors and TRP channels

[99] TRPA1 underlies a sensing mechanism for O2

[100] Reference: Channels: A TR(i)P in the air

[101] Reference: TRP channels: sensors and transducers of gasotransmitter signals

[102] Hypoxia-inducible factor-1α (HIF1α) switches on transient receptor potential ankyrin repeat 1 (TRPA1) gene expression via a hypoxia response element-like motif to modulate cytokine release

[103] Hypersensitivity of lung vagal C fibers induced by acute intermittent hypoxia in rats: role of reactive oxygen species and TRPA1

[104] TRP channels as sensors of oxygen availability

[105] Sensory Nerve Terminal Mitochondrial Dysfunction Activates Airway Sensory Nerves Via Transient Receptor Potential (TRP) Channels

[106] Role of Reactive Oxygen Species and Redox in Regulating the Function of Transient Receptor Potential Channels

[107] Sensory Nerve Terminal Mitochondrial Dysfunction Activates Airway Sensory Nerves Via Transient Receptor Potential (TRP) Channels

[108] Redox Regulation of Transient Receptor Potential Channels

[109] Transnitrosylation Directs TRPA1 Selectivity in N-Nitrosamine Activators

[110] Emerging roles of TRPA1 in sensation of oxidative stress and its implications in defense anddanger

[111] Transient Receptor Potential A1 Is a Sensory Receptor for Multiple Products of Oxidative Stress

[112] Pathophysiological roles of transient receptor potential channels in glial cells.

[113] Systematic and quantitative mRNA expression analysis of TRP channel genes at the single trigeminal and dorsal root ganglion level in mouse

[114] Reactive oxygen species enhance excitatory synaptic transmission in rat spinal dorsal horn neurons by activating TRPA1 and TRPV1 channels

[115] TRPV1, TRPA1, and CB1 in the isolated vagus nerve--axonal chemosensitivity and control of neuropeptide release

[116] Acrolein involvement in sensory and behavioral hypersensitivity following spinal cord injury in the rat

[117] Transient receptor potential A1 receptor-mediated neural cross-talk and afferent sensitization induced by oxidative stress: Implication for the pathogenesis of interstitial cystitis/bladder pain syndrome.

[118] Mechanisms of Disease: involvement of the urothelium in bladder dysfunction

[119] THE ROLE OF TRPA1 CHANNELS IN ACTIVATION OF SINGLE UNIT MECHANOSENSITIVE BLADDER AFFERENT ACTIVITIES IN THE RAT

[120] TRPA1 receptor modulation attenuates bladder overactivity induced by spinal cord injury

[121] Distribution and function of the hydrogen sulfide-sensitive TRPA1 ion channel in rat urinary bladder

[122] Antagonism of the transient receptor potential ankyrin 1 (TRPA1) attenuates hyperalgesia andurinary bladder overactivity in cyclophosphamide-induced haemorrhagic cystitis

[123] Transient receptor potential channels in bladder function

[124] Neurovascular Aspects of Skin Neurogenic Inflammation

[125] TRPA1 as an Analgesic Target

[126] Pharmacological blockade of TRPA1 inhibits mechanical firing in nociceptors

[127] Targeting TRP channels for pain relief

[128] TRP channels and analgesia

[129] Transient Receptor Potential Ankyrin 1 (TRPA1) Channel as Emerging Target for Novel Analgesics and Anti-Inflammatory Agents

[130] SuperPain—a resource on pain-relieving compounds targeting ion channels

[131] Transient receptor potential cation channels in disease.

[132] DYSREGULATED MRNAS MAY ALSO EXPLAIN COMMON CO-MORBIDITIES OF CFS

[133] TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades.

[134] Chapter 11 TRPA1 : A Sensory Channel of Many Talents

[135] The molecular basis for species-specific activation of human TRPA1 by protons involves poorly conserved residues within transmembrane domains 5 and 6

[136] ROLE OF TRP CHANNELS IN ENVIRONMENTAL IRRITANT-INDUCED HEADACHE DESCRIPTION

[137] POST-EXERCISE ION CHANNEL GENE EXPRESSION BIOMARKERS IN CFS

[138] NOVEL TRPA1 ANTAGONISTS

[139] Treatment of Respiratory Disorders using TRPA1 Antagonists

[140] PHARMACEUTICAL COMPOSITION COMPRISING A TRPA1 ANTAGONIST AND AN ANTICHOLINERGIC AGENT

[141] Heterocyclic amides as modulators of TRPA1

[142] Compounds useful for treating disorders related to TRPA1

[143] Modulation of TRP channels by resveratrol and other stilbenoids

[144] USE OF TRPA1 RECEPTOR ANTAGONISTS FOR TREATING DISEASES ASSOCIATED WITH BACTERIAL INFECTIONS

[145] Superpain database

TRPA1, LPS and the possible connection to ME symptoms

I would like to place this article
TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins
in the line of my reflections on ME/CFS/POTS/MCS-symptoms and TRPA1 activation.

Lipopolysaccharide (LPS) also known as bacterial endotoxins, and endogenous TRPA1 agonists have synergistic effects. Reactive oxygen species (ROS) are TRPA1 agonists.

If we combine this knowledge with the theory of central sensitization,

Excessive activation of TRPA1 and TRPV1 by ROS may induce central sensitization – does it concern ME?

we might understand why Maes and Leunis have helped ME/CFS patients by lowering the LPS burden:
Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria

LPS produces a strong fall in blood pressure within minutes of injection, and TRPA1 appears to participate in the vasodilation response to LPS. I have previously written about the hypothesis that TRPA1 could be involved in the co-morbidity POTS, because of this arcticle: 

Evidence for the pathophysiological relevance of TRPA1 receptors in the cardiovascular system in vivo:  "TRPA1 can also influence changes in blood pressure of possible relevance to autonomic system reflexes and potentially to vasovagal/neurocardiogenic syncope disorders".

Activation of TRPA1 is certainly involved in environmental exposure to chemicals:
Transient receptor potential channels and occupational exposure and Transient Receptor Potential in Multiple Chemical Sensitivity.

So, the question I keep coming back to: Is sustained firing of TRPA1 elicited by reactive agonists involved in ME symptoms? And will removal (reduction) of TRPA1 agonists attenuate ME symptoms?

Further reading on the subject:

Sustained firing of TRPA1 elicited by reactive agonists

Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome

LPS cause priming of microglia, and this may lead to progression of pre-existing neurodegenerative disease. Microglia priming - a role in ME?

Caveolae, eNOS and TRPA1?

Hvad betyder CD4+CD25+Tregs og FoxP3+Treg ekspression i ME/CFS?

ME/CFS patienter har signifikant højere niveau af CD4+CD25+Tregs og FoxP3+Treg ekspression. (1)

Det er lidt et paradoks, fordi det er normalt celler som er forbundet med regulering af immunforsvaret, så autoimmunitet ikke forekommer. Og ME/CFS er jo forbundet med mistanken om autoimmunitet.

Imidlertid er der vist ikke helt styr på betydningen af reguleringen af disse celler, idet  Tregs kan være dysreguleret - både op, ned og som forskellige typer - i autoimmune sygdomme som sclerose, type 1 diabetes, myasthenia gravis, lupus, rheumatoid arthritis og psoresasis. (2)

Men nu er der lige dukket en ny spændende artikel op, som får denne omtale:
Good guys gone bad: exTreg cells promote autoimmune arthritis

Her er selve artiklen:  Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis

Autoimmune sygdomme kan være et resultat af en ubalance mellem regulatoriske Treg og IL-17 producerende T helper TH17)  celler. FOXp3 er nødvendig for Tregs gode immunregulerende funktion. Men i ovenstående artikel har forskerne observeret, at de "gode fyre" er blevet til "de slemme" i den autoimmune sygdom kronisk leddegigt (rheumatoid arthritis).

Jeg er spændt på betydningen af denne artikel. Kunne denne viden være relevant i forhold til at forstå immundysreguleringen i ME/CFS?

Referencer:
(1) Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

(2) Imbalance of regulatory T cells in human autoimmune diseases