Allograft inflammatory factor-1 links T-cell activation, interferon response, and macrophage activation in chronic Kawasaki disease arteritis

Anne H Rowley*, Susan C. Baker, Kwang-Youn A Kim, Stanford T Shulman, Amy Yang, David Arrollo, Matthew DeBerge, Shuling Han, Nicholas E.S. Sibinga, Adam J. Pink, Edward Benjamin Thorp

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background. Kawasaki disease (KD) is widely viewed as an acute arteritis. However, our pathologic studies show that chronic coronary arteritis can persist long after disease onset and is closely linked with arterial stenosis. Transcriptome profiling of acute KD arteritis tissues revealed upregulation of T lymphocyte, type I interferon, and allograft inflammatory factor-1 (AIF1) genes. We determined whether these immune responses persist in chronic KD arteritis, and we investigated the role of AIF1 in these responses. Methods. Gene expression in chronic KD and childhood control arteries was determined by real-time reverse-transcriptase polymerase chain reaction, and arterial protein expression was determined by immunohistochemistry and immunofluorescence. Allograft inflammatory factor-1 small-interfering ribonucleic acid macrophage treatment was performed to investigate the role of AIF1 in macrophage and T lymphocyte activation. Results. Allograft inflammatory factor-1 protein was highly expressed in stenotic KD arteries and colocalized with the macrophage marker CD68. T lymphocyte and interferon pathway genes were significantly upregulated in chronic KD coronary artery tissues. Alpha interferon-induced macrophage expression of CD80 and major histocompatibility complex class II was dependent on AIF1, and macrophage expression of AIF1 was required for antigen-specific T lymphocyte activation. Conclusions. Allograft inflammatory factor-1, originally identified in posttransplant arterial stenosis, is markedly upregulated in KD stenotic arterial tissues. T lymphocyte and type I interferon responses persist in chronic KD arteritis. Allograft inflammatory factor-1 may play multiple roles linking type I interferon response, macrophage activation, and antigen-specific T lymphocyte activation. These results suggest the likely importance of lymphocyte-myeloid cell cross-talk in the pathogenesis of KD arteritis and can inform selection of new immunotherapies for clinical trials in high-risk KD children.

Original languageEnglish (US)
Pages (from-to)e94-e102
JournalJournal of the Pediatric Infectious Diseases Society
Volume6
Issue number3
DOIs
StatePublished - Sep 1 2017

Fingerprint

T Cell Transcription Factor 1
Arteritis
Mucocutaneous Lymph Node Syndrome
Macrophage Activation
Interferons
Allografts
Chronic Disease
T-Lymphocytes
Interferon Type I
Macrophages
Lymphocyte Activation
Pathologic Constriction
Arteries
Antigens
Gene Expression Profiling
Acute Disease
Myeloid Cells
Major Histocompatibility Complex
Reverse Transcriptase Polymerase Chain Reaction
Interferon-alpha

Keywords

  • Allograft inflammatory factor-1
  • Arteritis
  • Kawasaki disease

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Infectious Diseases

Cite this

@article{91a41a899c194fc2b62b69ab394c2c58,
title = "Allograft inflammatory factor-1 links T-cell activation, interferon response, and macrophage activation in chronic Kawasaki disease arteritis",
abstract = "Background. Kawasaki disease (KD) is widely viewed as an acute arteritis. However, our pathologic studies show that chronic coronary arteritis can persist long after disease onset and is closely linked with arterial stenosis. Transcriptome profiling of acute KD arteritis tissues revealed upregulation of T lymphocyte, type I interferon, and allograft inflammatory factor-1 (AIF1) genes. We determined whether these immune responses persist in chronic KD arteritis, and we investigated the role of AIF1 in these responses. Methods. Gene expression in chronic KD and childhood control arteries was determined by real-time reverse-transcriptase polymerase chain reaction, and arterial protein expression was determined by immunohistochemistry and immunofluorescence. Allograft inflammatory factor-1 small-interfering ribonucleic acid macrophage treatment was performed to investigate the role of AIF1 in macrophage and T lymphocyte activation. Results. Allograft inflammatory factor-1 protein was highly expressed in stenotic KD arteries and colocalized with the macrophage marker CD68. T lymphocyte and interferon pathway genes were significantly upregulated in chronic KD coronary artery tissues. Alpha interferon-induced macrophage expression of CD80 and major histocompatibility complex class II was dependent on AIF1, and macrophage expression of AIF1 was required for antigen-specific T lymphocyte activation. Conclusions. Allograft inflammatory factor-1, originally identified in posttransplant arterial stenosis, is markedly upregulated in KD stenotic arterial tissues. T lymphocyte and type I interferon responses persist in chronic KD arteritis. Allograft inflammatory factor-1 may play multiple roles linking type I interferon response, macrophage activation, and antigen-specific T lymphocyte activation. These results suggest the likely importance of lymphocyte-myeloid cell cross-talk in the pathogenesis of KD arteritis and can inform selection of new immunotherapies for clinical trials in high-risk KD children.",
keywords = "Allograft inflammatory factor-1, Arteritis, Kawasaki disease",
author = "Rowley, {Anne H} and Baker, {Susan C.} and Kim, {Kwang-Youn A} and Shulman, {Stanford T} and Amy Yang and David Arrollo and Matthew DeBerge and Shuling Han and Sibinga, {Nicholas E.S.} and Pink, {Adam J.} and Thorp, {Edward Benjamin}",
year = "2017",
month = "9",
day = "1",
doi = "10.1093/jpids/pix025",
language = "English (US)",
volume = "6",
pages = "e94--e102",
journal = "Journal of the Pediatric Infectious Diseases Society",
issn = "2048-7207",
publisher = "Oxford University Press",
number = "3",

}

Allograft inflammatory factor-1 links T-cell activation, interferon response, and macrophage activation in chronic Kawasaki disease arteritis. / Rowley, Anne H; Baker, Susan C.; Kim, Kwang-Youn A; Shulman, Stanford T; Yang, Amy; Arrollo, David; DeBerge, Matthew; Han, Shuling; Sibinga, Nicholas E.S.; Pink, Adam J.; Thorp, Edward Benjamin.

In: Journal of the Pediatric Infectious Diseases Society, Vol. 6, No. 3, 01.09.2017, p. e94-e102.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Allograft inflammatory factor-1 links T-cell activation, interferon response, and macrophage activation in chronic Kawasaki disease arteritis

AU - Rowley, Anne H

AU - Baker, Susan C.

AU - Kim, Kwang-Youn A

AU - Shulman, Stanford T

AU - Yang, Amy

AU - Arrollo, David

AU - DeBerge, Matthew

AU - Han, Shuling

AU - Sibinga, Nicholas E.S.

AU - Pink, Adam J.

AU - Thorp, Edward Benjamin

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Background. Kawasaki disease (KD) is widely viewed as an acute arteritis. However, our pathologic studies show that chronic coronary arteritis can persist long after disease onset and is closely linked with arterial stenosis. Transcriptome profiling of acute KD arteritis tissues revealed upregulation of T lymphocyte, type I interferon, and allograft inflammatory factor-1 (AIF1) genes. We determined whether these immune responses persist in chronic KD arteritis, and we investigated the role of AIF1 in these responses. Methods. Gene expression in chronic KD and childhood control arteries was determined by real-time reverse-transcriptase polymerase chain reaction, and arterial protein expression was determined by immunohistochemistry and immunofluorescence. Allograft inflammatory factor-1 small-interfering ribonucleic acid macrophage treatment was performed to investigate the role of AIF1 in macrophage and T lymphocyte activation. Results. Allograft inflammatory factor-1 protein was highly expressed in stenotic KD arteries and colocalized with the macrophage marker CD68. T lymphocyte and interferon pathway genes were significantly upregulated in chronic KD coronary artery tissues. Alpha interferon-induced macrophage expression of CD80 and major histocompatibility complex class II was dependent on AIF1, and macrophage expression of AIF1 was required for antigen-specific T lymphocyte activation. Conclusions. Allograft inflammatory factor-1, originally identified in posttransplant arterial stenosis, is markedly upregulated in KD stenotic arterial tissues. T lymphocyte and type I interferon responses persist in chronic KD arteritis. Allograft inflammatory factor-1 may play multiple roles linking type I interferon response, macrophage activation, and antigen-specific T lymphocyte activation. These results suggest the likely importance of lymphocyte-myeloid cell cross-talk in the pathogenesis of KD arteritis and can inform selection of new immunotherapies for clinical trials in high-risk KD children.

AB - Background. Kawasaki disease (KD) is widely viewed as an acute arteritis. However, our pathologic studies show that chronic coronary arteritis can persist long after disease onset and is closely linked with arterial stenosis. Transcriptome profiling of acute KD arteritis tissues revealed upregulation of T lymphocyte, type I interferon, and allograft inflammatory factor-1 (AIF1) genes. We determined whether these immune responses persist in chronic KD arteritis, and we investigated the role of AIF1 in these responses. Methods. Gene expression in chronic KD and childhood control arteries was determined by real-time reverse-transcriptase polymerase chain reaction, and arterial protein expression was determined by immunohistochemistry and immunofluorescence. Allograft inflammatory factor-1 small-interfering ribonucleic acid macrophage treatment was performed to investigate the role of AIF1 in macrophage and T lymphocyte activation. Results. Allograft inflammatory factor-1 protein was highly expressed in stenotic KD arteries and colocalized with the macrophage marker CD68. T lymphocyte and interferon pathway genes were significantly upregulated in chronic KD coronary artery tissues. Alpha interferon-induced macrophage expression of CD80 and major histocompatibility complex class II was dependent on AIF1, and macrophage expression of AIF1 was required for antigen-specific T lymphocyte activation. Conclusions. Allograft inflammatory factor-1, originally identified in posttransplant arterial stenosis, is markedly upregulated in KD stenotic arterial tissues. T lymphocyte and type I interferon responses persist in chronic KD arteritis. Allograft inflammatory factor-1 may play multiple roles linking type I interferon response, macrophage activation, and antigen-specific T lymphocyte activation. These results suggest the likely importance of lymphocyte-myeloid cell cross-talk in the pathogenesis of KD arteritis and can inform selection of new immunotherapies for clinical trials in high-risk KD children.

KW - Allograft inflammatory factor-1

KW - Arteritis

KW - Kawasaki disease

UR - http://www.scopus.com/inward/record.url?scp=85030471593&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85030471593&partnerID=8YFLogxK

U2 - 10.1093/jpids/pix025

DO - 10.1093/jpids/pix025

M3 - Article

C2 - 28505365

AN - SCOPUS:85030471593

VL - 6

SP - e94-e102

JO - Journal of the Pediatric Infectious Diseases Society

JF - Journal of the Pediatric Infectious Diseases Society

SN - 2048-7207

IS - 3

ER -