Deficient tryptophan catabolism along the kynurenine pathway reveals that the epididymis is in a unique tolerogenic state

Aicha Jrad-Lamine, Joelle Henry-Berger, Pascal Gourbeyre, Christelle Damon-Soubeyrand, Alain Lenoir, Lydie Combaret, Fabrice Saez, Ayhan Kocer, Shigenobu Tone, Dietmar Fuchs, Wentao Zhu, Peter J. Oefner, David H. Munn, Andrew L. Mellor, Najoua Gharbi, Rémi Cadet, R. John Aitken, Joël R. Dreveta

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Indoleamine 2,3-dioxygenase (IDO) is the first and rate-limiting enzyme of tryptophan catabolism through the kynurenine pathway. Intriguingly, IDO is constitutively and highly expressed in the mammalian epididymis in contrast to most other tissues where IDO is induced by proinflammatory cytokines, such as interferons. To gain insight into the role of IDO in the physiology of the mammalian epididymis, we studied both wild type and Ido1-/--deficient mice. In the caput epididymis of. Ido1-/- animals, the lack of IDO activity was not compensated by other tryptophan-catabolizing enzymes and led to the loss of kynurenine production. The absence of IDO generated an inflammatory state in the caput epididymis as revealed by an increased accumulation of various inflammation markers. The absence of IDO also increased the tryptophan content of the caput epididymis and generated a parallel increase in caput epididymal protein content as a consequence of deficient proteasomal activity. Surprisingly, the lack of IDO expression had no noticeable impact on overall male fertility but did induce highly significant increases in both the number and the percentage of abnormal spermatozoa. These changes coincided with a significant decrease in white blood cell count in epididymal fluid compared with wild type mice. These data provide support for IDO playing a hitherto unsuspected role in sperm quality control in the epididymis involving the ubiquitination of defective spermatozoa and their subsequent removal.

Original languageEnglish (US)
Pages (from-to)8030-8042
Number of pages13
JournalJournal of Biological Chemistry
Volume286
Issue number10
DOIs
StatePublished - Mar 11 2011

Fingerprint

Indoleamine-Pyrrole 2,3,-Dioxygenase
Kynurenine
Epididymis
Tryptophan
Spermatozoa
Ubiquitination
Physiology
Enzymes
Leukocyte Count
Quality Control
Interferons
Quality control
Fertility
Animals
Blood
Cells
Tissue
Cytokines
Inflammation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Jrad-Lamine, A., Henry-Berger, J., Gourbeyre, P., Damon-Soubeyrand, C., Lenoir, A., Combaret, L., ... Dreveta, J. R. (2011). Deficient tryptophan catabolism along the kynurenine pathway reveals that the epididymis is in a unique tolerogenic state. Journal of Biological Chemistry, 286(10), 8030-8042. https://doi.org/10.1074/jbc.M110.172114

Deficient tryptophan catabolism along the kynurenine pathway reveals that the epididymis is in a unique tolerogenic state. / Jrad-Lamine, Aicha; Henry-Berger, Joelle; Gourbeyre, Pascal; Damon-Soubeyrand, Christelle; Lenoir, Alain; Combaret, Lydie; Saez, Fabrice; Kocer, Ayhan; Tone, Shigenobu; Fuchs, Dietmar; Zhu, Wentao; Oefner, Peter J.; Munn, David H.; Mellor, Andrew L.; Gharbi, Najoua; Cadet, Rémi; Aitken, R. John; Dreveta, Joël R.

In: Journal of Biological Chemistry, Vol. 286, No. 10, 11.03.2011, p. 8030-8042.

Research output: Contribution to journalArticle

Jrad-Lamine, A, Henry-Berger, J, Gourbeyre, P, Damon-Soubeyrand, C, Lenoir, A, Combaret, L, Saez, F, Kocer, A, Tone, S, Fuchs, D, Zhu, W, Oefner, PJ, Munn, DH, Mellor, AL, Gharbi, N, Cadet, R, Aitken, RJ & Dreveta, JR 2011, 'Deficient tryptophan catabolism along the kynurenine pathway reveals that the epididymis is in a unique tolerogenic state', Journal of Biological Chemistry, vol. 286, no. 10, pp. 8030-8042. https://doi.org/10.1074/jbc.M110.172114
Jrad-Lamine, Aicha ; Henry-Berger, Joelle ; Gourbeyre, Pascal ; Damon-Soubeyrand, Christelle ; Lenoir, Alain ; Combaret, Lydie ; Saez, Fabrice ; Kocer, Ayhan ; Tone, Shigenobu ; Fuchs, Dietmar ; Zhu, Wentao ; Oefner, Peter J. ; Munn, David H. ; Mellor, Andrew L. ; Gharbi, Najoua ; Cadet, Rémi ; Aitken, R. John ; Dreveta, Joël R. / Deficient tryptophan catabolism along the kynurenine pathway reveals that the epididymis is in a unique tolerogenic state. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 10. pp. 8030-8042.
@article{4d45bbc56fa049108fd6d398fe2416b8,
title = "Deficient tryptophan catabolism along the kynurenine pathway reveals that the epididymis is in a unique tolerogenic state",
abstract = "Indoleamine 2,3-dioxygenase (IDO) is the first and rate-limiting enzyme of tryptophan catabolism through the kynurenine pathway. Intriguingly, IDO is constitutively and highly expressed in the mammalian epididymis in contrast to most other tissues where IDO is induced by proinflammatory cytokines, such as interferons. To gain insight into the role of IDO in the physiology of the mammalian epididymis, we studied both wild type and Ido1-/--deficient mice. In the caput epididymis of. Ido1-/- animals, the lack of IDO activity was not compensated by other tryptophan-catabolizing enzymes and led to the loss of kynurenine production. The absence of IDO generated an inflammatory state in the caput epididymis as revealed by an increased accumulation of various inflammation markers. The absence of IDO also increased the tryptophan content of the caput epididymis and generated a parallel increase in caput epididymal protein content as a consequence of deficient proteasomal activity. Surprisingly, the lack of IDO expression had no noticeable impact on overall male fertility but did induce highly significant increases in both the number and the percentage of abnormal spermatozoa. These changes coincided with a significant decrease in white blood cell count in epididymal fluid compared with wild type mice. These data provide support for IDO playing a hitherto unsuspected role in sperm quality control in the epididymis involving the ubiquitination of defective spermatozoa and their subsequent removal.",
author = "Aicha Jrad-Lamine and Joelle Henry-Berger and Pascal Gourbeyre and Christelle Damon-Soubeyrand and Alain Lenoir and Lydie Combaret and Fabrice Saez and Ayhan Kocer and Shigenobu Tone and Dietmar Fuchs and Wentao Zhu and Oefner, {Peter J.} and Munn, {David H.} and Mellor, {Andrew L.} and Najoua Gharbi and R{\'e}mi Cadet and Aitken, {R. John} and Dreveta, {Jo{\"e}l R.}",
year = "2011",
month = "3",
day = "11",
doi = "10.1074/jbc.M110.172114",
language = "English (US)",
volume = "286",
pages = "8030--8042",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "10",

}

TY - JOUR

T1 - Deficient tryptophan catabolism along the kynurenine pathway reveals that the epididymis is in a unique tolerogenic state

AU - Jrad-Lamine, Aicha

AU - Henry-Berger, Joelle

AU - Gourbeyre, Pascal

AU - Damon-Soubeyrand, Christelle

AU - Lenoir, Alain

AU - Combaret, Lydie

AU - Saez, Fabrice

AU - Kocer, Ayhan

AU - Tone, Shigenobu

AU - Fuchs, Dietmar

AU - Zhu, Wentao

AU - Oefner, Peter J.

AU - Munn, David H.

AU - Mellor, Andrew L.

AU - Gharbi, Najoua

AU - Cadet, Rémi

AU - Aitken, R. John

AU - Dreveta, Joël R.

PY - 2011/3/11

Y1 - 2011/3/11

N2 - Indoleamine 2,3-dioxygenase (IDO) is the first and rate-limiting enzyme of tryptophan catabolism through the kynurenine pathway. Intriguingly, IDO is constitutively and highly expressed in the mammalian epididymis in contrast to most other tissues where IDO is induced by proinflammatory cytokines, such as interferons. To gain insight into the role of IDO in the physiology of the mammalian epididymis, we studied both wild type and Ido1-/--deficient mice. In the caput epididymis of. Ido1-/- animals, the lack of IDO activity was not compensated by other tryptophan-catabolizing enzymes and led to the loss of kynurenine production. The absence of IDO generated an inflammatory state in the caput epididymis as revealed by an increased accumulation of various inflammation markers. The absence of IDO also increased the tryptophan content of the caput epididymis and generated a parallel increase in caput epididymal protein content as a consequence of deficient proteasomal activity. Surprisingly, the lack of IDO expression had no noticeable impact on overall male fertility but did induce highly significant increases in both the number and the percentage of abnormal spermatozoa. These changes coincided with a significant decrease in white blood cell count in epididymal fluid compared with wild type mice. These data provide support for IDO playing a hitherto unsuspected role in sperm quality control in the epididymis involving the ubiquitination of defective spermatozoa and their subsequent removal.

AB - Indoleamine 2,3-dioxygenase (IDO) is the first and rate-limiting enzyme of tryptophan catabolism through the kynurenine pathway. Intriguingly, IDO is constitutively and highly expressed in the mammalian epididymis in contrast to most other tissues where IDO is induced by proinflammatory cytokines, such as interferons. To gain insight into the role of IDO in the physiology of the mammalian epididymis, we studied both wild type and Ido1-/--deficient mice. In the caput epididymis of. Ido1-/- animals, the lack of IDO activity was not compensated by other tryptophan-catabolizing enzymes and led to the loss of kynurenine production. The absence of IDO generated an inflammatory state in the caput epididymis as revealed by an increased accumulation of various inflammation markers. The absence of IDO also increased the tryptophan content of the caput epididymis and generated a parallel increase in caput epididymal protein content as a consequence of deficient proteasomal activity. Surprisingly, the lack of IDO expression had no noticeable impact on overall male fertility but did induce highly significant increases in both the number and the percentage of abnormal spermatozoa. These changes coincided with a significant decrease in white blood cell count in epididymal fluid compared with wild type mice. These data provide support for IDO playing a hitherto unsuspected role in sperm quality control in the epididymis involving the ubiquitination of defective spermatozoa and their subsequent removal.

UR - http://www.scopus.com/inward/record.url?scp=79953149140&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953149140&partnerID=8YFLogxK

U2 - 10.1074/jbc.M110.172114

DO - 10.1074/jbc.M110.172114

M3 - Article

C2 - 21189261

AN - SCOPUS:79953149140

VL - 286

SP - 8030

EP - 8042

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 10

ER -