Abstract
The emergence of new regulatory and pro-inflammatory immune cell subsets and cytokines dictates the need to re-examine the role of these subsets in various diseases involving the immune system. IL-17 has been recently identified as a key cytokine involved in numerous autoimmune processes. However, its role in liver autoimmune diseases remains unclear. Primary biliary cirrhosis (PBC) is characterized histologically by autoreactive CD4 and CD8 T cells surrounding damaged bile ducts. CD4+ T cells are a major source of IL-17, which compose a distinct T helper subset (Th17). Thus we set out to determine the role of IL-17 in both human and a murine model of PBC in a liver-targeted manner. Our data demonstrate an increase in the frequency of IL-17+ lymphocytic infiltration in liver tissues from PBC patients and those with other liver dysfunctions as compared to healthy livers. IL-2 receptor α knockout mice, a recently identified murine model of human PBC, also demonstrate marked aggregations of IL-17-positive cells within portal tracts and increased frequencies of Th17 cells in the liver compared to the periphery. Interestingly, CD4+ T cells from livers of normal C57BL/6J mice also secreted higher levels of IL-17 relative to those from spleens, indicating a preferential induction of Th17 cells in liver tissues. Importantly, C57BL/6J cocultures of splenic CD4+ T cells and liver non-parenchymal cells increased IL-17 production approximately 10-fold compared to T cells alone, suggesting a role of the liver microenvironment in Th17 induction in cases of liver autoimmunity and other liver inflammatory diseases.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 43-51 |
| Number of pages | 9 |
| Journal | Journal of Autoimmunity |
| Volume | 32 |
| Issue number | 1 |
| DOIs | |
| State | Published - Feb 2009 |
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Keywords
- CD46
- CD T cells
- IL-17
- IL-2 receptor alpha
- Liver
- Microenvironment
- Primary biliary cirrhosis
- Tr1
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
Hepatic IL-17 responses in human and murine primary biliary cirrhosis. / Lan, Ruth Y Z; Salunga, Thucydides L.; Tsuneyama, Koichi; Lian, Zhe Xiong; Yang, Guo Xiang; Hsu, Willy; Moritoki, Yuki; Ansari, Aftab A.; Kemper, Claudia; Price, Jeff; Atkinson, John P.; Coppel, Ross L.; Gershwin, M. Eric.
In: Journal of Autoimmunity, Vol. 32, No. 1, 02.2009, p. 43-51.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hepatic IL-17 responses in human and murine primary biliary cirrhosis
AU - Lan, Ruth Y Z
AU - Salunga, Thucydides L.
AU - Tsuneyama, Koichi
AU - Lian, Zhe Xiong
AU - Yang, Guo Xiang
AU - Hsu, Willy
AU - Moritoki, Yuki
AU - Ansari, Aftab A.
AU - Kemper, Claudia
AU - Price, Jeff
AU - Atkinson, John P.
AU - Coppel, Ross L.
AU - Gershwin, M. Eric
PY - 2009/2
Y1 - 2009/2
N2 - The emergence of new regulatory and pro-inflammatory immune cell subsets and cytokines dictates the need to re-examine the role of these subsets in various diseases involving the immune system. IL-17 has been recently identified as a key cytokine involved in numerous autoimmune processes. However, its role in liver autoimmune diseases remains unclear. Primary biliary cirrhosis (PBC) is characterized histologically by autoreactive CD4 and CD8 T cells surrounding damaged bile ducts. CD4+ T cells are a major source of IL-17, which compose a distinct T helper subset (Th17). Thus we set out to determine the role of IL-17 in both human and a murine model of PBC in a liver-targeted manner. Our data demonstrate an increase in the frequency of IL-17+ lymphocytic infiltration in liver tissues from PBC patients and those with other liver dysfunctions as compared to healthy livers. IL-2 receptor α knockout mice, a recently identified murine model of human PBC, also demonstrate marked aggregations of IL-17-positive cells within portal tracts and increased frequencies of Th17 cells in the liver compared to the periphery. Interestingly, CD4+ T cells from livers of normal C57BL/6J mice also secreted higher levels of IL-17 relative to those from spleens, indicating a preferential induction of Th17 cells in liver tissues. Importantly, C57BL/6J cocultures of splenic CD4+ T cells and liver non-parenchymal cells increased IL-17 production approximately 10-fold compared to T cells alone, suggesting a role of the liver microenvironment in Th17 induction in cases of liver autoimmunity and other liver inflammatory diseases.
AB - The emergence of new regulatory and pro-inflammatory immune cell subsets and cytokines dictates the need to re-examine the role of these subsets in various diseases involving the immune system. IL-17 has been recently identified as a key cytokine involved in numerous autoimmune processes. However, its role in liver autoimmune diseases remains unclear. Primary biliary cirrhosis (PBC) is characterized histologically by autoreactive CD4 and CD8 T cells surrounding damaged bile ducts. CD4+ T cells are a major source of IL-17, which compose a distinct T helper subset (Th17). Thus we set out to determine the role of IL-17 in both human and a murine model of PBC in a liver-targeted manner. Our data demonstrate an increase in the frequency of IL-17+ lymphocytic infiltration in liver tissues from PBC patients and those with other liver dysfunctions as compared to healthy livers. IL-2 receptor α knockout mice, a recently identified murine model of human PBC, also demonstrate marked aggregations of IL-17-positive cells within portal tracts and increased frequencies of Th17 cells in the liver compared to the periphery. Interestingly, CD4+ T cells from livers of normal C57BL/6J mice also secreted higher levels of IL-17 relative to those from spleens, indicating a preferential induction of Th17 cells in liver tissues. Importantly, C57BL/6J cocultures of splenic CD4+ T cells and liver non-parenchymal cells increased IL-17 production approximately 10-fold compared to T cells alone, suggesting a role of the liver microenvironment in Th17 induction in cases of liver autoimmunity and other liver inflammatory diseases.
KW - CD46
KW - CD T cells
KW - IL-17
KW - IL-2 receptor alpha
KW - Liver
KW - Microenvironment
KW - Primary biliary cirrhosis
KW - Tr1
UR - http://www.scopus.com/inward/record.url?scp=58849115337&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=58849115337&partnerID=8YFLogxK
U2 - 10.1016/j.jaut.2008.11.001
DO - 10.1016/j.jaut.2008.11.001
M3 - Article
C2 - 19101114
AN - SCOPUS:58849115337
VL - 32
SP - 43
EP - 51
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
SN - 0896-8411
IS - 1
ER -