Amplification of autoimmune response through induction of dendritic cell maturation in inflamed tissues

Kristin Melli, Rachel S. Friedman, Ashley E. Martin, Erik B. Finger, Gang Miao, Gregory L. Szot, Matthew F. Krummel, Qizhi Tang

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Dendritic cells (DCs) are essential in T cell-mediated destruction of insulin-producing β cells in the islets of Langerhans in type 1 diabetes. In this study, we investigated T cell induction of intra-islet DC maturation during the progression of the disease in both autoimmune-prone NOD and resistant C57BL/6 mice. We demonstrated steady-state capture and retention of unprocessed β cell-derived proteins by semimature intra-islet DCs in both mouse strains. T cell-mediated intra-islet inflammation induced an increase in CD40 and CD80 expression and processing of captured Ag by resident DCs without inducing the expression of the p40 subunit of IL-12/23. Some of the CD40 high intra-islet DCs up-regulated CCR7, and a small number of CD40high DCs bearing unprocessed islet Ags were detected in the pancreatic lymph nodes in mice with acute intra-islet inflammation, demonstrating that T cell-mediated tissue inflammation augments migration of mature resident DCs to draining lymph nodes. Our results identify an amplification loop during the progression of autoimmune diabetes, in which initial T cell infiltration leads to rapid maturation of intra-islet DCs, their migration to lymph nodes, and expanded priming of more autoreactive T cells. Therapeutic interventions that intercept this process may be effective at halting the progression of type 1 diabetes.

Original languageEnglish (US)
Pages (from-to)2590-2600
Number of pages11
JournalJournal of Immunology
Volume182
Issue number5
DOIs
StatePublished - Mar 1 2009

Fingerprint

Autoimmunity
Dendritic Cells
Islets of Langerhans
T-Lymphocytes
Type 1 Diabetes Mellitus
Lymph Nodes
Inflammation
Interleukin-23
Interleukin-12
Inbred C57BL Mouse
Cell Movement
Disease Progression
Insulin
Proteins

Cite this

Amplification of autoimmune response through induction of dendritic cell maturation in inflamed tissues. / Melli, Kristin; Friedman, Rachel S.; Martin, Ashley E.; Finger, Erik B.; Miao, Gang; Szot, Gregory L.; Krummel, Matthew F.; Tang, Qizhi.

In: Journal of Immunology, Vol. 182, No. 5, 01.03.2009, p. 2590-2600.

Research output: Contribution to journalArticle

Melli, K, Friedman, RS, Martin, AE, Finger, EB, Miao, G, Szot, GL, Krummel, MF & Tang, Q 2009, 'Amplification of autoimmune response through induction of dendritic cell maturation in inflamed tissues', Journal of Immunology, vol. 182, no. 5, pp. 2590-2600. https://doi.org/10.4049/jimmunol.0803543
Melli, Kristin ; Friedman, Rachel S. ; Martin, Ashley E. ; Finger, Erik B. ; Miao, Gang ; Szot, Gregory L. ; Krummel, Matthew F. ; Tang, Qizhi. / Amplification of autoimmune response through induction of dendritic cell maturation in inflamed tissues. In: Journal of Immunology. 2009 ; Vol. 182, No. 5. pp. 2590-2600.
@article{f753901794774dfc9bfefeffc98cca8b,
title = "Amplification of autoimmune response through induction of dendritic cell maturation in inflamed tissues",
abstract = "Dendritic cells (DCs) are essential in T cell-mediated destruction of insulin-producing β cells in the islets of Langerhans in type 1 diabetes. In this study, we investigated T cell induction of intra-islet DC maturation during the progression of the disease in both autoimmune-prone NOD and resistant C57BL/6 mice. We demonstrated steady-state capture and retention of unprocessed β cell-derived proteins by semimature intra-islet DCs in both mouse strains. T cell-mediated intra-islet inflammation induced an increase in CD40 and CD80 expression and processing of captured Ag by resident DCs without inducing the expression of the p40 subunit of IL-12/23. Some of the CD40 high intra-islet DCs up-regulated CCR7, and a small number of CD40high DCs bearing unprocessed islet Ags were detected in the pancreatic lymph nodes in mice with acute intra-islet inflammation, demonstrating that T cell-mediated tissue inflammation augments migration of mature resident DCs to draining lymph nodes. Our results identify an amplification loop during the progression of autoimmune diabetes, in which initial T cell infiltration leads to rapid maturation of intra-islet DCs, their migration to lymph nodes, and expanded priming of more autoreactive T cells. Therapeutic interventions that intercept this process may be effective at halting the progression of type 1 diabetes.",
author = "Kristin Melli and Friedman, {Rachel S.} and Martin, {Ashley E.} and Finger, {Erik B.} and Gang Miao and Szot, {Gregory L.} and Krummel, {Matthew F.} and Qizhi Tang",
year = "2009",
month = "3",
day = "1",
doi = "10.4049/jimmunol.0803543",
language = "English (US)",
volume = "182",
pages = "2590--2600",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "5",

}

TY - JOUR

T1 - Amplification of autoimmune response through induction of dendritic cell maturation in inflamed tissues

AU - Melli, Kristin

AU - Friedman, Rachel S.

AU - Martin, Ashley E.

AU - Finger, Erik B.

AU - Miao, Gang

AU - Szot, Gregory L.

AU - Krummel, Matthew F.

AU - Tang, Qizhi

PY - 2009/3/1

Y1 - 2009/3/1

N2 - Dendritic cells (DCs) are essential in T cell-mediated destruction of insulin-producing β cells in the islets of Langerhans in type 1 diabetes. In this study, we investigated T cell induction of intra-islet DC maturation during the progression of the disease in both autoimmune-prone NOD and resistant C57BL/6 mice. We demonstrated steady-state capture and retention of unprocessed β cell-derived proteins by semimature intra-islet DCs in both mouse strains. T cell-mediated intra-islet inflammation induced an increase in CD40 and CD80 expression and processing of captured Ag by resident DCs without inducing the expression of the p40 subunit of IL-12/23. Some of the CD40 high intra-islet DCs up-regulated CCR7, and a small number of CD40high DCs bearing unprocessed islet Ags were detected in the pancreatic lymph nodes in mice with acute intra-islet inflammation, demonstrating that T cell-mediated tissue inflammation augments migration of mature resident DCs to draining lymph nodes. Our results identify an amplification loop during the progression of autoimmune diabetes, in which initial T cell infiltration leads to rapid maturation of intra-islet DCs, their migration to lymph nodes, and expanded priming of more autoreactive T cells. Therapeutic interventions that intercept this process may be effective at halting the progression of type 1 diabetes.

AB - Dendritic cells (DCs) are essential in T cell-mediated destruction of insulin-producing β cells in the islets of Langerhans in type 1 diabetes. In this study, we investigated T cell induction of intra-islet DC maturation during the progression of the disease in both autoimmune-prone NOD and resistant C57BL/6 mice. We demonstrated steady-state capture and retention of unprocessed β cell-derived proteins by semimature intra-islet DCs in both mouse strains. T cell-mediated intra-islet inflammation induced an increase in CD40 and CD80 expression and processing of captured Ag by resident DCs without inducing the expression of the p40 subunit of IL-12/23. Some of the CD40 high intra-islet DCs up-regulated CCR7, and a small number of CD40high DCs bearing unprocessed islet Ags were detected in the pancreatic lymph nodes in mice with acute intra-islet inflammation, demonstrating that T cell-mediated tissue inflammation augments migration of mature resident DCs to draining lymph nodes. Our results identify an amplification loop during the progression of autoimmune diabetes, in which initial T cell infiltration leads to rapid maturation of intra-islet DCs, their migration to lymph nodes, and expanded priming of more autoreactive T cells. Therapeutic interventions that intercept this process may be effective at halting the progression of type 1 diabetes.

UR - http://www.scopus.com/inward/record.url?scp=64849085429&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=64849085429&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.0803543

DO - 10.4049/jimmunol.0803543

M3 - Article

VL - 182

SP - 2590

EP - 2600

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 5

ER -