Tissue Transglutaminase Appears in Monocytes and Macrophages but Not in Lymphocytes in White Matter Multiple Sclerosis Lesions

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Abstract

Leukocyte infiltration is an important pathological hallmark of multiple sclerosis (MS) and is therefore targeted by current MS therapies. The enzyme tissue transglutaminase (TG2) contributes to monocyte/macrophage migration and is present in MS lesions and could be a potential therapeutic target. We examined the cellular identity of TG2-expressing cells by immunohistochemistry in white matter lesions of 13 MS patients; 9 active and chronic active lesions from 4 patients were analyzed in detail. In these active MS lesions, TG2 is predominantly expressed in leukocytes (CD45 þ) but not in cells of the lymphocyte lineage, that is, T cells (CD3 þ) and B cells (CD20 þ). In general, cells of the monocyte/macrophage lineage (CD11b þor CD68 þ) are TG2 þbut no further distinction could be made regarding pro- or anti-inflammatory macrophage subtypes. In conclusion, TG2 is abundantly present in cells of the monocyte/macrophage lineage in active white matter MS lesions. We consider that TG2 can play a role in MS as it is associated with macrophage infiltration into the CNS. As such, TG2 potentially presents a novel target for therapeutic intervention that can support available MS therapies targeting lymphocyte infiltration.

Original languageEnglish
Pages (from-to)492-500
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Volume78
Issue number6
DOIs
Publication statusPublished - 1 Jan 2019

Cite this

@article{edaff0bbf6dc401984333228326efc6e,
title = "Tissue Transglutaminase Appears in Monocytes and Macrophages but Not in Lymphocytes in White Matter Multiple Sclerosis Lesions",
abstract = "Leukocyte infiltration is an important pathological hallmark of multiple sclerosis (MS) and is therefore targeted by current MS therapies. The enzyme tissue transglutaminase (TG2) contributes to monocyte/macrophage migration and is present in MS lesions and could be a potential therapeutic target. We examined the cellular identity of TG2-expressing cells by immunohistochemistry in white matter lesions of 13 MS patients; 9 active and chronic active lesions from 4 patients were analyzed in detail. In these active MS lesions, TG2 is predominantly expressed in leukocytes (CD45 {\th}) but not in cells of the lymphocyte lineage, that is, T cells (CD3 {\th}) and B cells (CD20 {\th}). In general, cells of the monocyte/macrophage lineage (CD11b {\th}or CD68 {\th}) are TG2 {\th}but no further distinction could be made regarding pro- or anti-inflammatory macrophage subtypes. In conclusion, TG2 is abundantly present in cells of the monocyte/macrophage lineage in active white matter MS lesions. We consider that TG2 can play a role in MS as it is associated with macrophage infiltration into the CNS. As such, TG2 potentially presents a novel target for therapeutic intervention that can support available MS therapies targeting lymphocyte infiltration.",
keywords = "Leukocytes, Macrophages, Monocytes, Multiple sclerosis, Tissue transglutaminase",
author = "Chrobok, {Navina L.} and Bol, {John G. J. M.} and Wilhelmus, {Micha M. M.} and Benjamin Drukarch and {van Dam}, Anne-Marie",
year = "2019",
month = "1",
day = "1",
doi = "10.1093/jnen/nlz030",
language = "English",
volume = "78",
pages = "492--500",
journal = "Journal of Neuropathology and Experimental Neurology",
issn = "0022-3069",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Tissue Transglutaminase Appears in Monocytes and Macrophages but Not in Lymphocytes in White Matter Multiple Sclerosis Lesions

AU - Chrobok, Navina L.

AU - Bol, John G. J. M.

AU - Wilhelmus, Micha M. M.

AU - Drukarch, Benjamin

AU - van Dam, Anne-Marie

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Leukocyte infiltration is an important pathological hallmark of multiple sclerosis (MS) and is therefore targeted by current MS therapies. The enzyme tissue transglutaminase (TG2) contributes to monocyte/macrophage migration and is present in MS lesions and could be a potential therapeutic target. We examined the cellular identity of TG2-expressing cells by immunohistochemistry in white matter lesions of 13 MS patients; 9 active and chronic active lesions from 4 patients were analyzed in detail. In these active MS lesions, TG2 is predominantly expressed in leukocytes (CD45 þ) but not in cells of the lymphocyte lineage, that is, T cells (CD3 þ) and B cells (CD20 þ). In general, cells of the monocyte/macrophage lineage (CD11b þor CD68 þ) are TG2 þbut no further distinction could be made regarding pro- or anti-inflammatory macrophage subtypes. In conclusion, TG2 is abundantly present in cells of the monocyte/macrophage lineage in active white matter MS lesions. We consider that TG2 can play a role in MS as it is associated with macrophage infiltration into the CNS. As such, TG2 potentially presents a novel target for therapeutic intervention that can support available MS therapies targeting lymphocyte infiltration.

AB - Leukocyte infiltration is an important pathological hallmark of multiple sclerosis (MS) and is therefore targeted by current MS therapies. The enzyme tissue transglutaminase (TG2) contributes to monocyte/macrophage migration and is present in MS lesions and could be a potential therapeutic target. We examined the cellular identity of TG2-expressing cells by immunohistochemistry in white matter lesions of 13 MS patients; 9 active and chronic active lesions from 4 patients were analyzed in detail. In these active MS lesions, TG2 is predominantly expressed in leukocytes (CD45 þ) but not in cells of the lymphocyte lineage, that is, T cells (CD3 þ) and B cells (CD20 þ). In general, cells of the monocyte/macrophage lineage (CD11b þor CD68 þ) are TG2 þbut no further distinction could be made regarding pro- or anti-inflammatory macrophage subtypes. In conclusion, TG2 is abundantly present in cells of the monocyte/macrophage lineage in active white matter MS lesions. We consider that TG2 can play a role in MS as it is associated with macrophage infiltration into the CNS. As such, TG2 potentially presents a novel target for therapeutic intervention that can support available MS therapies targeting lymphocyte infiltration.

KW - Leukocytes

KW - Macrophages

KW - Monocytes

KW - Multiple sclerosis

KW - Tissue transglutaminase

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UR - https://www.ncbi.nlm.nih.gov/pubmed/31058279

U2 - 10.1093/jnen/nlz030

DO - 10.1093/jnen/nlz030

M3 - Article

VL - 78

SP - 492

EP - 500

JO - Journal of Neuropathology and Experimental Neurology

JF - Journal of Neuropathology and Experimental Neurology

SN - 0022-3069

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