Targeting pyruvate kinase M2 (PKM2) reduces T cell pathogenicity in multiple sclerosis.

Elena Ellmeier; Alyssa Schnabl; J Meissel; Anika Stracke; Sonja Rittchen; CA Passegger; Cansu Tafrali; Rina Demjaha; Maria Martinez Serrat; T Kaiser; L Zeiler; K Seifried; A Topler; Bettina Heschl; Anna Damulina; Marah Runtsch; Johannes Fessler; Edith Hofer; Michael Khalil; Stefano Angiari

doi:10.1016/j.ebiom.2026.106314

Targeting pyruvate kinase M2 (PKM2) reduces T cell pathogenicity in multiple sclerosis.

Elena Ellmeier (Erstautor*in)
, Alyssa Schnabl
, J Meissel
, Anika Stracke
, Sonja Rittchen
, CA Passegger
, Cansu Tafrali
, Rina Demjaha
, Maria Martinez Serrat
, T Kaiser
, L Zeiler
, K Seifried
, A Topler
, Bettina Heschl
, Anna Damulina
, Marah Runtsch
, Johannes Fessler
, Edith Hofer
, Michael Khalil^*
, Stefano Angiari^*

^*Korrespondierende/r Autor/-in für diese Arbeit

Publikation: Beitrag in Fachzeitschrift › Originalarbeit

Abstract

BACKGROUND: Pyruvate kinase M2 (PKM2) is an enzyme with moonlighting activities that controls murine T cell pro-inflammatory potential in a mouse model of multiple sclerosis (MS). However, no study analysed in detail the expression of PKM2 in human T cell subsets, and whether targeting PKM2 may limit the inflammatory potential of T cells from patients with MS is unknown.

METHODS: In this observational, case control study we evaluated the expression of PKM2 in circulating T cells of healthy control individuals (HCs) and patients with MS, as well as its isomerisation in peripheral blood mononuclear cells (PBMCs) from HCs and patients. In parallel, we analysed the impact of targeting PKM2 on the inflammatory profile of T cells from HCs and individuals with MS.

FINDINGS: Circulating effector and memory T cells express higher PKM2 levels compared to naïve T cells, and PKM2 expression in such T cell subsets may correlate with age and disease duration in individuals with MS. Among effector/memory T cells, the Th17/Tc17 subsets display the highest PKM2 expression. Additionally, we observed a preferential inhibition of interferon-gamma (IFN-γ), interleukin-5 (IL-5), IL-13, and IL-17 production by MS T cells upon PKM2 pharmacological targeting. Finally, we found that PBMCs from patients with MS have a higher percentage of PKM2 monomer compared to PBMCs from HCs, supporting heightened PKM2 moonlighting activity.

INTERPRETATION: Our data suggest that PKM2 may represent a therapeutic target to limit T cell-driven inflammation in MS and potentially other human autoimmune diseases.

FUNDING: Austrian Multiple Sclerosis Research Society, Kulturamt der Stadt Graz, MEFOGraz and Worldwide Cancer Research.

Originalsprache	Englisch
Aufsatznummer	106314
Seiten (von - bis)	106314
Seitenumfang	21
Fachzeitschrift	eBioMedicine
Jahrgang	128
DOIs	https://doi.org/10.1016/j.ebiom.2026.106314
Publikationsstatus	Veröffentlicht - Juni 2026

UN SDGs

Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung

SDG 3 – Gute Gesundheit und Wohlergehen

Wissenschaftszweige

301 Medizinisch-theoretische Wissenschaften, Pharmazie
302 Klinische Medizin

Zugriff auf Dokument

10.1016/j.ebiom.2026.106314

Andere Dateien und Links

Dieses zitieren

Ellmeier, E., Schnabl, A., Meissel, J., Stracke, A., Rittchen, S., Passegger, CA., Tafrali, C., Demjaha, R., Martinez Serrat, M., Kaiser, T., Zeiler, L., Seifried, K., Topler, A., Heschl, B., Damulina, A., Runtsch, M., Fessler, J., Hofer, E., Khalil, M., & Angiari, S. (2026). Targeting pyruvate kinase M2 (PKM2) reduces T cell pathogenicity in multiple sclerosis. eBioMedicine, 128, 106314. Artikel 106314. https://doi.org/10.1016/j.ebiom.2026.106314

@article{50f20f8cab2c45658c0bb0e0ebd53325,

title = "Targeting pyruvate kinase M2 (PKM2) reduces T cell pathogenicity in multiple sclerosis.",

abstract = "BACKGROUND: Pyruvate kinase M2 (PKM2) is an enzyme with moonlighting activities that controls murine T cell pro-inflammatory potential in a mouse model of multiple sclerosis (MS). However, no study analysed in detail the expression of PKM2 in human T cell subsets, and whether targeting PKM2 may limit the inflammatory potential of T cells from patients with MS is unknown.METHODS: In this observational, case control study we evaluated the expression of PKM2 in circulating T cells of healthy control individuals (HCs) and patients with MS, as well as its isomerisation in peripheral blood mononuclear cells (PBMCs) from HCs and patients. In parallel, we analysed the impact of targeting PKM2 on the inflammatory profile of T cells from HCs and individuals with MS.FINDINGS: Circulating effector and memory T cells express higher PKM2 levels compared to na{\"i}ve T cells, and PKM2 expression in such T cell subsets may correlate with age and disease duration in individuals with MS. Among effector/memory T cells, the Th17/Tc17 subsets display the highest PKM2 expression. Additionally, we observed a preferential inhibition of interferon-gamma (IFN-γ), interleukin-5 (IL-5), IL-13, and IL-17 production by MS T cells upon PKM2 pharmacological targeting. Finally, we found that PBMCs from patients with MS have a higher percentage of PKM2 monomer compared to PBMCs from HCs, supporting heightened PKM2 moonlighting activity.INTERPRETATION: Our data suggest that PKM2 may represent a therapeutic target to limit T cell-driven inflammation in MS and potentially other human autoimmune diseases.FUNDING: Austrian Multiple Sclerosis Research Society, Kulturamt der Stadt Graz, MEFOGraz and Worldwide Cancer Research.",

author = "Elena Ellmeier and Alyssa Schnabl and J Meissel and Anika Stracke and Sonja Rittchen and CA Passegger and Cansu Tafrali and Rina Demjaha and \{Martinez Serrat\}, Maria and T Kaiser and L Zeiler and K Seifried and A Topler and Bettina Heschl and Anna Damulina and Marah Runtsch and Johannes Fessler and Edith Hofer and Michael Khalil and Stefano Angiari",

year = "2026",

month = jun,

doi = "10.1016/j.ebiom.2026.106314",

language = "English",

volume = "128",

pages = "106314",

journal = "eBioMedicine",

issn = "2352-3964",

publisher = "Elsevier B.V.",

}

Ellmeier, E , Schnabl, A, Meissel, J, Stracke, A , Rittchen, S, Passegger, CA, Tafrali, C , Demjaha, R , Martinez Serrat, M, Kaiser, T, Zeiler, L, Seifried, K, Topler, A, Heschl, B , Damulina, A, Runtsch, M, Fessler, J , Hofer, E , Khalil, M & Angiari, S 2026, 'Targeting pyruvate kinase M2 (PKM2) reduces T cell pathogenicity in multiple sclerosis.', eBioMedicine, Jg. 128, 106314, S. 106314. https://doi.org/10.1016/j.ebiom.2026.106314

TY - JOUR

T1 - Targeting pyruvate kinase M2 (PKM2) reduces T cell pathogenicity in multiple sclerosis.

AU - Schnabl, Alyssa

AU - Meissel, J

AU - Stracke, Anika

AU - Rittchen, Sonja

AU - Passegger, CA

AU - Tafrali, Cansu

AU - Demjaha, Rina

AU - Martinez Serrat, Maria

AU - Kaiser, T

AU - Zeiler, L

AU - Seifried, K

AU - Topler, A

AU - Heschl, Bettina

AU - Damulina, Anna

AU - Runtsch, Marah

AU - Fessler, Johannes

AU - Hofer, Edith

AU - Khalil, Michael

AU - Angiari, Stefano

A2 - Ellmeier, Elena

PY - 2026/6

Y1 - 2026/6

N2 - BACKGROUND: Pyruvate kinase M2 (PKM2) is an enzyme with moonlighting activities that controls murine T cell pro-inflammatory potential in a mouse model of multiple sclerosis (MS). However, no study analysed in detail the expression of PKM2 in human T cell subsets, and whether targeting PKM2 may limit the inflammatory potential of T cells from patients with MS is unknown.METHODS: In this observational, case control study we evaluated the expression of PKM2 in circulating T cells of healthy control individuals (HCs) and patients with MS, as well as its isomerisation in peripheral blood mononuclear cells (PBMCs) from HCs and patients. In parallel, we analysed the impact of targeting PKM2 on the inflammatory profile of T cells from HCs and individuals with MS.FINDINGS: Circulating effector and memory T cells express higher PKM2 levels compared to naïve T cells, and PKM2 expression in such T cell subsets may correlate with age and disease duration in individuals with MS. Among effector/memory T cells, the Th17/Tc17 subsets display the highest PKM2 expression. Additionally, we observed a preferential inhibition of interferon-gamma (IFN-γ), interleukin-5 (IL-5), IL-13, and IL-17 production by MS T cells upon PKM2 pharmacological targeting. Finally, we found that PBMCs from patients with MS have a higher percentage of PKM2 monomer compared to PBMCs from HCs, supporting heightened PKM2 moonlighting activity.INTERPRETATION: Our data suggest that PKM2 may represent a therapeutic target to limit T cell-driven inflammation in MS and potentially other human autoimmune diseases.FUNDING: Austrian Multiple Sclerosis Research Society, Kulturamt der Stadt Graz, MEFOGraz and Worldwide Cancer Research.

AB - BACKGROUND: Pyruvate kinase M2 (PKM2) is an enzyme with moonlighting activities that controls murine T cell pro-inflammatory potential in a mouse model of multiple sclerosis (MS). However, no study analysed in detail the expression of PKM2 in human T cell subsets, and whether targeting PKM2 may limit the inflammatory potential of T cells from patients with MS is unknown.METHODS: In this observational, case control study we evaluated the expression of PKM2 in circulating T cells of healthy control individuals (HCs) and patients with MS, as well as its isomerisation in peripheral blood mononuclear cells (PBMCs) from HCs and patients. In parallel, we analysed the impact of targeting PKM2 on the inflammatory profile of T cells from HCs and individuals with MS.FINDINGS: Circulating effector and memory T cells express higher PKM2 levels compared to naïve T cells, and PKM2 expression in such T cell subsets may correlate with age and disease duration in individuals with MS. Among effector/memory T cells, the Th17/Tc17 subsets display the highest PKM2 expression. Additionally, we observed a preferential inhibition of interferon-gamma (IFN-γ), interleukin-5 (IL-5), IL-13, and IL-17 production by MS T cells upon PKM2 pharmacological targeting. Finally, we found that PBMCs from patients with MS have a higher percentage of PKM2 monomer compared to PBMCs from HCs, supporting heightened PKM2 moonlighting activity.INTERPRETATION: Our data suggest that PKM2 may represent a therapeutic target to limit T cell-driven inflammation in MS and potentially other human autoimmune diseases.FUNDING: Austrian Multiple Sclerosis Research Society, Kulturamt der Stadt Graz, MEFOGraz and Worldwide Cancer Research.

UR - https://pubmed.ncbi.nlm.nih.gov/42208151

UR - https://pmc.ncbi.nlm.nih.gov/articles/PMC13235379

U2 - 10.1016/j.ebiom.2026.106314

DO - 10.1016/j.ebiom.2026.106314

M3 - Research article

C2 - 42208151

SN - 2352-3964

VL - 128

SP - 106314

JO - eBioMedicine

JF - eBioMedicine

M1 - 106314

ER -

Targeting pyruvate kinase M2 (PKM2) reduces T cell pathogenicity in multiple sclerosis.

Abstract

UN SDGs

Wissenschaftszweige

Zugriff auf Dokument

Andere Dateien und Links

Fingerprint

Dieses zitieren