Balloon cells promote immune system activation in focal cortical dysplasia type 2b › Research Explorer (2023)

Balloon cells promote activation of the immune system in focal cortical dysplasia type 2b./Zimmer, Till S.; Broekaart, Diede W. M.; Luinenburg, Mark et al.

Em:Neuropathology and Applied Neurobiology, Bd. 47, Nr. 6, 10.2021, S. 826-839.

search result:contribution to the journal›Article›academic›Peer-Review

Zimmer, TS, Broekart, D.W.M, Luinenburg, M, Mijnsbergen, C, Anink, JJ, Sim, NS, Michaelidou, I, Jansen, FE, van Rijen, PC, Lee, JH, François, L, van Eyll, J, Dedeurwaerdere, S, vanVliet, EA, Mühlebner, A, Mills, JD2021, 'Balloon cells promote activation of the immune system in focal cortical dysplasia type 2b',Neuropathology and Applied Neurobiology, vol. 47, no. 6, pp. 826-839.https://doi.org/10.1111/nan.12736

Zimmer, T. S., Broekaart, D.W.M., Luinenburg, M., Mijnsbergen, C., Anink, J. J., I, N.S., Michailidou, I., Jansen, F. E., van Rijen, P. C., Lee, J. H., François, L., van Eyll, J., Dedeurwaerdere, S., van Vliet, E.A., Mühlebner, A., Mills, J. D.(2021).Balloon cells promote activation of the immune system in focal cortical dysplasia type 2b.Neuropathology and Applied Neurobiology,47(6), 826-839.https://doi.org/10.1111/nan.12736

Zimmer TS, Broekart DWM, Luinenburg M, Mijnsbergen C, Anink JJ, SimNS et al.Balloon cells promote activation of the immune system in focal cortical dysplasia type 2b.Neuropathology and Applied Neurobiology. 2021 Aug;47(6):826-839. Epub 2021. doi: 10.1111/nan.12736

Zimmer, Till S. ; Broekaart, Diede W. M.; Luinenburg, Mark et al. /Balloon cells promote activation of the immune system in focal cortical dysplasia type 2b. Em:Neuropathology and Applied Neurobiology. 2021; Bd. 47, Nr. 6. S. 826-839.

@artigo{5726b8813e2b4d2988b33c2c2110b6e4,

title = "Balloon cells promote immune system activation in focal cortical dysplasia type 2b",

abstract = "Objectives: Focal cortical dysplasia (FCD) type 2 is an epileptogenic malformation of the neocortex associated with somatic mutations in the rapamycin target (mTOR) signaling pathway in mammals. Although activation of the proepileptogenic immune system and inflammatory reactions are common in both It is not known what contextual role BCs play.METHODS: The present study used RNA sequencing of surgically resected brain tissue from patients with FCD 2a (n=11) and FCD 2b (n=20) compared to autopsy controls (n = 9) focusing on three processes of the immune system: adaptive immunity, innate immunity, and cytokine production.This analysis was followed by immunohistochemistry in a clinically well-characterized FCD-2 cohort.Results: Analysis of differential expression revealed greater expression of components of the innate Immunity, adaptive immunity and cytokine production in FCD 2b than in FCD 2a, specifically complement activation and antigen presentation. Immunohistochemical analysis confirmed these results with strong expression of leukocyte antigens I and II in FCD 2b compared to FCD 2a. In addition, tissue infiltration of T lymphocytes was increased in FCD 2b. Expression of markers of immune system activation in FCD 2b was concentrated in the subcortical white matter. Finally, antigen presentation strongly correlated with BC load in FCD-2b lesions. Conclusion: We conclude that BCs are critical drivers of inflammation in FCD 2b, along with mTOR activation and mutational seizure activity. "Our results suggest that pro-inflammatory therapies may be of benefit in FCD 2b,"

Keywords = "balloon cells, focal cortical dysplasia, immune system, inflammation",

Author = "Zimmer, {Till S.} and Broekart, {Diede W. M.} and Mark Luinenburg and Caroline Mijnsbergen and Anink, {Jasper J.} and Sim, {Nam Suk} and Iliana Michailidou and Jansen, {Floor E.} and {van Rijen}, {Peter C.} and Lee, {Jeong Ho} and Liesbeth Fran{\c}ois and {van Eyll}, Jonathan and Stefanie Dedeurwaedere and {van Vliet}, {Erwin A.} and Angelika M{ "u}hlebner and Mills, {James D.} and Eleonora Aronica",

nota="Funding Information: LF, JVE and SD were employees of UCB Pharma at the time of the research. AE and JM are funded by an unrestricted grant from UCB Pharma. Funding Information: The research leading to these results was funded by the Seventh Framework Programme of the European Union (FP7/2007-2013) under Grant Agreements No. 602391 (EPISTOP; EA, FJ) and No. 602102 (EPITARGET; EAvV, EA), the European Union Horizon 2020 AMLO-05-2020 ?Twinning (EpiEpiNet; EA, EAvV), grant agreement no. 952455, Dutch Epilepsy Foundation, project numbers 16-05, 20-11 (DWMB, EAvV) and 20-02 (AM, ML); Horizon 2020 research of the European Union and innovation program under the Marie- Sklodowska-Curie Grant Agreement No. 722053 (EU-GliaPhD; TSZ, EA); ZonMw, Translational Research Program No. 95105004 (EA); An unrestricted grant from UCB Pharma (AE, JM); Prinses Beatrix Spierfonds, Grant Application No.: W.OR14 to Frank Baas (IM) Funding information: The research leading to these results was funded by the European Union's Seventh Framework Program {\textquoteight} ( FP7/2007–2013 ) under grant agreement no. 602391 (EPISTOP; EA, FJ) and no. 602102 (EPITARGET; EAvV, EA), European Union{\textquoteright}s Horizon 2020 WIDESPREAD‐05‐2020–Twinning (EpiEpiNet; EA, EAvV), grant agreement no. 952455, Dutch Epilepsy Foundation, project numbers 16-05, 20-11 (DWMB, EAvV) and 20-02 (AM, ML); The European Union's Horizon 2020 research and innovation program under Marie Sklodowska-Curie grant agreement No. 722053 (EU-GliaPhD; TSZ, EA); ZonMw, Translational Research Program No. 95105004 (EA); an unrestricted grant from UCB Pharma (AE, JM); Princesses Beatrix Spierfonds, grant application no.: W.OR14 to Frank Baas (IM). Publisher Copyright: {\textcopyright} 2021 The Authors. Neuropathology and Applied Neurobiology, published by John Wiley & Sons Ltd on behalf of the British Neuropathological Society. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.”,

again = "2021",

month = october,

two = "10.1111/in.12736",

language="English",

volume = "47",

pages="826--839",

Journal = "Neuropathology and Applied Neurobiology",

issn = „0305-1846“,

Publisher = "Wiley-Blackwell",

number = "6",

}

YOU - DIA

T1 – Balloon cells promote activation of the immune system in focal cortical dysplasia type 2b

AU - Zimmer, Till S.

AU - Bridge-Karte, Diede W. M.

AU - Luinenburg, Mark

AU – Mijnsbergen, Caroline

AU-Anink, Jasper J.

AU - Sim, Nam Suk

AU – Michailidou, Iliana

AU - Jansen, Piso E.

AU - van Rijen, Peter C.

AU – Lee, Jeong Ho

AU - Francois, Liesbeth

AU – van Eyll, Jonathan

AU - Dedeurwaedere, Stefanie

AU - van Vliet, Erwin A.

AU - Mühlebner, Angelika

AU-Mills, James D.

AU - Aronica, Eleonora

N1 - Funding Information: LF, JVE and SD were employees of UCB Pharma at the time of the survey. AE and JM are financially supported by an unrestricted grant from UCB Pharma. Funding Information: The research leading to these results was funded by the European Union's Seventh Framework Program (FP7/2007-2013) under grant agreement no. 602391 (EPISTOP; EA, FJ) and no. 602102 (EPITARGET; EAvV, EA), Horizon 2020 WIDESPREAD-05-2020?Twinning of the European Union (EpiEpiNet; EA, EAvV), grant agreement no. 952455, Dutch Epilepsy Foundation, project numbers 16-05, 20-11 (DWMB, EAvV) and 20-02 (AM, ML); the European Union Horizon 2020 research and innovation program under Marie Sklodowska-Curie grant contract No. 722053 (EU-GliaPhD; TSZ, EA); ZonMw, Translational Research Program No. 95105004 (EA); an unrestricted grant from UCB Pharma (AE, JM); Prinses Beatrix Spierfonds, grant application no.: W.OR14 to Frank Baas (IM). 602391 (EPISTOP; EA, FJ) and #602102 (EPITARGET; EAvV, EA), European Union Horizon 2020 WIDESPREAD‐05‐2020–Twinning (EpiEpiNet; EA, EAvV), Grant Agreement #952455, Dutch Epilepsy Foundation, project number 16 -05, 20-11 (DWMB, EAvV) and 20-02 (AM, ML); The European Union's Horizon 2020 research and innovation program under Marie Sklodowska-Curie grant agreement No. 722053 (EU-GliaPhD; TSZ, EA); ZonMw, Translational Research Program No. 95105004 (EA); an unrestricted grant from UCB Pharma (AE, JM); Prinses Beatrix Spierfonds, grant application no.: W.OR14 to Frank Baas (IM). Publisher Copyright: © 2021 The Authors. Neuropathology and applied neurobiology. Published by John Wiley & Sons Ltd on behalf of the British Neuropathological Society. Copyright: Copyright 2021 Elsevier B.V., all rights reserved.

Fiscal year - 2021/10

A1 – 2021/10

N2 - Objectives: Focal cortical dysplasia (FCD) type 2 is an epileptogenic malformation of the neocortex associated with somatic mutations in the mammalian rapamycin targeting pathway (mTOR). Histopathologically, FCD 2 is divided into FCD 2a and FCD 2b, with the only distinguishing feature being the presence of balloon cells (BCs) in FCD 2b. Although activation of the proepileptogenic immune system and inflammatory responses are common in both subtypes, the contextual role of BCs is unknown. Methods: The present study used RNA sequencing of surgically resected brain tissue from patients with FCD 2a (n=11) and FCD 2b (n=20) versus autopsy controls (n=9), focusing on three immune system processes : adaptive immunity, innate immunity and cytokine production. This analysis was followed by immunohistochemistry in a clinically well-characterized FCD-2 cohort. Results: Differential expression analysis revealed a higher expression of components of innate immunity, adaptive immunity and cytokine production in FCD 2b than in FCD 2a, in particular complement activation and antigen presentation. Immunohistochemical analysis confirmed these results with strong expression of leukocyte antigens I and II in FCD 2b compared to FCD 2a. In addition, tissue infiltration of T lymphocytes was increased in FCD 2b. Expression of markers of immune system activation in FCD 2b was concentrated in the subcortical white matter. Finally, antigen presentation strongly correlated with BC load in FCD-2b lesions. Conclusion: We conclude that BCs are critical drivers of inflammation in FCD 2b, along with mTOR activation and mutational seizure activity. Our results suggest that pro-inflammatory therapies may be beneficial in FCD 2b.

AB - Objectives: Focal cortical dysplasia (FCD) type 2 is an epileptogenic malformation of the neocortex associated with somatic mutations in the mammalian rapamycin targeting pathway (mTOR). Histopathologically, FCD 2 is divided into FCD 2a and FCD 2b, with the only distinguishing feature being the presence of balloon cells (BCs) in FCD 2b. Although activation of the proepileptogenic immune system and inflammatory responses are common in both subtypes, the contextual role of BCs is unknown. Methods: The present study used RNA sequencing of surgically resected brain tissue from patients with FCD 2a (n=11) and FCD 2b (n=20) versus autopsy controls (n=9), focusing on three immune system processes : adaptive immunity, innate immunity and cytokine production. This analysis was followed by immunohistochemistry in a clinically well-characterized FCD-2 cohort. Results: Differential expression analysis revealed a higher expression of components of innate immunity, adaptive immunity and cytokine production in FCD 2b than in FCD 2a, in particular complement activation and antigen presentation. Immunohistochemical analysis confirmed these results with strong expression of leukocyte antigens I and II in FCD 2b compared to FCD 2a. In addition, tissue infiltration of T lymphocytes was increased in FCD 2b. Expression of markers of immune system activation in FCD 2b was concentrated in the subcortical white matter. Finally, antigen presentation strongly correlated with BC load in FCD-2b lesions. Conclusion: We conclude that BCs are critical drivers of inflammation in FCD 2b, along with mTOR activation and mutational seizure activity. Our results suggest that pro-inflammatory therapies may be beneficial in FCD 2b.

KW - balloon cells

KW – cortical focal Dysplasia

KW - immune system

KW - inflammation

UR – http://www.scopus.com/inward/record.url?scp=85107551902&partnerID=8YFLogxK

U2 – 10,1111/in.12736

DO-10.1111/nan.12736

M3 - artillery

C2 - 34003514

VL - 47

SP - 826

EP - 839

JO - Neuropathology and Applied Neurobiology

JF - Neuropathology and Applied Neurobiology

SN - 0305-1846

IS - 6

AND -