T cell targeting and phagocytosis of apoptotic biliary epithelial cells in primary biliary cirrhosis

Jorge Allina, Bin Hu, Daniel M. Sullivan, Maria Isabel Fiel, Swan N. Thung, Steven F. Bronk, Robert C Huebert, Judy van de Water, Nicholas F La Russo, M. E. Gershwin, Gregory James Gores, Joseph A. Odin

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Primary biliary cirrhosis (PBC) is characterized by loss of tolerance against ubiquitously expressed mitochondrial autoantigens followed by biliary and salivary gland epithelial cell (BEC and SGEC) destruction by autoreactive T cells. It is unclear why BECs and SGECs are targeted. Previous work demonstrated that the reduced form of the major PBC autoantigen predominated in apoptotic BECs and SGECs as opposed to an oxidized form in other apoptotic cells. This led to the hypothesis that presentation of novel self-peptides from phagocytosed apoptotic BECs might contribute to BEC targeting by autoreactive T cells. The effect of autoantigen redox status on self-peptide formation was examined along with the phagocytic ability of BECs. Oxidation of PBC autoantigens first was shown to be due to protein S-glutathionylation of lipoyllysine residues. Absence of protein S-glutathionylation generated novel self-peptides and affected T cell recognition of a lipoyllysine containing peptide. Liver biopsy staining revealed BEC phagocytosis of apoptotic BECs (3.74 ± 2.90% of BEC) was present in PBC (7 of 7 cases) but not in normal livers (0 of 3). BECs have the ability to present novel mitochondrial self-peptides derived from phagocytosed apoptotic BECs. Apoptotic cell phagocytosis by non-professional phagocytes may influence the tissue specificity of autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)232-241
Number of pages10
JournalJournal of Autoimmunity
Volume27
Issue number4
DOIs
StatePublished - Dec 2006

Fingerprint

Cytophagocytosis
Biliary Liver Cirrhosis
Autoantigens
Epithelial Cells
Phagocytosis
T-Lymphocytes
Peptides
Protein S
Peptide T
Organ Specificity
Liver
Phagocytes
Salivary Glands
Autoimmune Diseases
Oxidation-Reduction
Staining and Labeling
Biopsy
lipoyllysine

Keywords

  • Apoptosis
  • Autoantigen
  • Primary biliary cirrhosis
  • Protein S-glutathionylation
  • Pyruvate dehydrogenase

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Allina, J., Hu, B., Sullivan, D. M., Fiel, M. I., Thung, S. N., Bronk, S. F., ... Odin, J. A. (2006). T cell targeting and phagocytosis of apoptotic biliary epithelial cells in primary biliary cirrhosis. Journal of Autoimmunity, 27(4), 232-241. https://doi.org/10.1016/j.jaut.2006.11.004

T cell targeting and phagocytosis of apoptotic biliary epithelial cells in primary biliary cirrhosis. / Allina, Jorge; Hu, Bin; Sullivan, Daniel M.; Fiel, Maria Isabel; Thung, Swan N.; Bronk, Steven F.; Huebert, Robert C; van de Water, Judy; La Russo, Nicholas F; Gershwin, M. E.; Gores, Gregory James; Odin, Joseph A.

In: Journal of Autoimmunity, Vol. 27, No. 4, 12.2006, p. 232-241.

Research output: Contribution to journalArticle

Allina, J, Hu, B, Sullivan, DM, Fiel, MI, Thung, SN, Bronk, SF, Huebert, RC, van de Water, J, La Russo, NF, Gershwin, ME, Gores, GJ & Odin, JA 2006, 'T cell targeting and phagocytosis of apoptotic biliary epithelial cells in primary biliary cirrhosis', Journal of Autoimmunity, vol. 27, no. 4, pp. 232-241. https://doi.org/10.1016/j.jaut.2006.11.004
Allina, Jorge ; Hu, Bin ; Sullivan, Daniel M. ; Fiel, Maria Isabel ; Thung, Swan N. ; Bronk, Steven F. ; Huebert, Robert C ; van de Water, Judy ; La Russo, Nicholas F ; Gershwin, M. E. ; Gores, Gregory James ; Odin, Joseph A. / T cell targeting and phagocytosis of apoptotic biliary epithelial cells in primary biliary cirrhosis. In: Journal of Autoimmunity. 2006 ; Vol. 27, No. 4. pp. 232-241.
@article{651cfe706e39429bb8fa0ca79261bde4,
title = "T cell targeting and phagocytosis of apoptotic biliary epithelial cells in primary biliary cirrhosis",
abstract = "Primary biliary cirrhosis (PBC) is characterized by loss of tolerance against ubiquitously expressed mitochondrial autoantigens followed by biliary and salivary gland epithelial cell (BEC and SGEC) destruction by autoreactive T cells. It is unclear why BECs and SGECs are targeted. Previous work demonstrated that the reduced form of the major PBC autoantigen predominated in apoptotic BECs and SGECs as opposed to an oxidized form in other apoptotic cells. This led to the hypothesis that presentation of novel self-peptides from phagocytosed apoptotic BECs might contribute to BEC targeting by autoreactive T cells. The effect of autoantigen redox status on self-peptide formation was examined along with the phagocytic ability of BECs. Oxidation of PBC autoantigens first was shown to be due to protein S-glutathionylation of lipoyllysine residues. Absence of protein S-glutathionylation generated novel self-peptides and affected T cell recognition of a lipoyllysine containing peptide. Liver biopsy staining revealed BEC phagocytosis of apoptotic BECs (3.74 ± 2.90{\%} of BEC) was present in PBC (7 of 7 cases) but not in normal livers (0 of 3). BECs have the ability to present novel mitochondrial self-peptides derived from phagocytosed apoptotic BECs. Apoptotic cell phagocytosis by non-professional phagocytes may influence the tissue specificity of autoimmune diseases.",
keywords = "Apoptosis, Autoantigen, Primary biliary cirrhosis, Protein S-glutathionylation, Pyruvate dehydrogenase",
author = "Jorge Allina and Bin Hu and Sullivan, {Daniel M.} and Fiel, {Maria Isabel} and Thung, {Swan N.} and Bronk, {Steven F.} and Huebert, {Robert C} and {van de Water}, Judy and {La Russo}, {Nicholas F} and Gershwin, {M. E.} and Gores, {Gregory James} and Odin, {Joseph A.}",
year = "2006",
month = "12",
doi = "10.1016/j.jaut.2006.11.004",
language = "English (US)",
volume = "27",
pages = "232--241",
journal = "Journal of Autoimmunity",
issn = "0896-8411",
publisher = "Academic Press Inc.",
number = "4",

}

TY - JOUR

T1 - T cell targeting and phagocytosis of apoptotic biliary epithelial cells in primary biliary cirrhosis

AU - Allina, Jorge

AU - Hu, Bin

AU - Sullivan, Daniel M.

AU - Fiel, Maria Isabel

AU - Thung, Swan N.

AU - Bronk, Steven F.

AU - Huebert, Robert C

AU - van de Water, Judy

AU - La Russo, Nicholas F

AU - Gershwin, M. E.

AU - Gores, Gregory James

AU - Odin, Joseph A.

PY - 2006/12

Y1 - 2006/12

N2 - Primary biliary cirrhosis (PBC) is characterized by loss of tolerance against ubiquitously expressed mitochondrial autoantigens followed by biliary and salivary gland epithelial cell (BEC and SGEC) destruction by autoreactive T cells. It is unclear why BECs and SGECs are targeted. Previous work demonstrated that the reduced form of the major PBC autoantigen predominated in apoptotic BECs and SGECs as opposed to an oxidized form in other apoptotic cells. This led to the hypothesis that presentation of novel self-peptides from phagocytosed apoptotic BECs might contribute to BEC targeting by autoreactive T cells. The effect of autoantigen redox status on self-peptide formation was examined along with the phagocytic ability of BECs. Oxidation of PBC autoantigens first was shown to be due to protein S-glutathionylation of lipoyllysine residues. Absence of protein S-glutathionylation generated novel self-peptides and affected T cell recognition of a lipoyllysine containing peptide. Liver biopsy staining revealed BEC phagocytosis of apoptotic BECs (3.74 ± 2.90% of BEC) was present in PBC (7 of 7 cases) but not in normal livers (0 of 3). BECs have the ability to present novel mitochondrial self-peptides derived from phagocytosed apoptotic BECs. Apoptotic cell phagocytosis by non-professional phagocytes may influence the tissue specificity of autoimmune diseases.

AB - Primary biliary cirrhosis (PBC) is characterized by loss of tolerance against ubiquitously expressed mitochondrial autoantigens followed by biliary and salivary gland epithelial cell (BEC and SGEC) destruction by autoreactive T cells. It is unclear why BECs and SGECs are targeted. Previous work demonstrated that the reduced form of the major PBC autoantigen predominated in apoptotic BECs and SGECs as opposed to an oxidized form in other apoptotic cells. This led to the hypothesis that presentation of novel self-peptides from phagocytosed apoptotic BECs might contribute to BEC targeting by autoreactive T cells. The effect of autoantigen redox status on self-peptide formation was examined along with the phagocytic ability of BECs. Oxidation of PBC autoantigens first was shown to be due to protein S-glutathionylation of lipoyllysine residues. Absence of protein S-glutathionylation generated novel self-peptides and affected T cell recognition of a lipoyllysine containing peptide. Liver biopsy staining revealed BEC phagocytosis of apoptotic BECs (3.74 ± 2.90% of BEC) was present in PBC (7 of 7 cases) but not in normal livers (0 of 3). BECs have the ability to present novel mitochondrial self-peptides derived from phagocytosed apoptotic BECs. Apoptotic cell phagocytosis by non-professional phagocytes may influence the tissue specificity of autoimmune diseases.

KW - Apoptosis

KW - Autoantigen

KW - Primary biliary cirrhosis

KW - Protein S-glutathionylation

KW - Pyruvate dehydrogenase

UR - http://www.scopus.com/inward/record.url?scp=33846699177&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846699177&partnerID=8YFLogxK

U2 - 10.1016/j.jaut.2006.11.004

DO - 10.1016/j.jaut.2006.11.004

M3 - Article

VL - 27

SP - 232

EP - 241

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

SN - 0896-8411

IS - 4

ER -