Glt25d2 Knockout Directly Increases CD25+CD69- but Decreases CD25-CD69+ Subset Proliferation and is Involved in Concanavalin-Induced Hepatitis.

Abstract

BACKGROUND/AIMS:

The elaborate structure of the extracellular matrix (ECM) and the appropriate surface glycoforms upon it are indispensable to CD4+ T cell regulation.

METHODS:

To explore the effects of Glcα1,2Galβ1 glycosylation mediated by GLT25D2 (Colgalt2) for CD4+ T cell regulation, we prepared C57BL/6J Glt25d2-/- mice. In the induction of hepatitis, after concanavalin A (Con A) challenge for 6, 12, and 24 h, more extensive parenchymal injury was noted in Glt25d2-/- mice than in wild-type (WT) mice at 12 h. Immunohistochemistry and laser scanning confocal microscopy were used to detect GLT25D2 expression, and subsets of CD4+T cells was analyzed by flow cytometry. A total of 26 cytokines in serum samples were determined using Luminex technology.

RESULTS:

The trend in liver injury score variation was consistent with serum alanine aminotransferase and aspartate aminotransferase levels. The levels of interleukin 4 (IL-4), IL-1β, IL-9, and several chemokines such as macrophage inflammatory protein-2, eotaxin, and growth-related oncogene α were significantly increased in Glt25d2-/- mice compared with WT mice after Con A challenge. A further phenotype analysis of primary Glt25d2-/- CD4+ T cells showed that Glt25d2 knockout increased the frequency of the CD25+CD69- subset but decreased the frequency of the CD25-CD69+ subset after Con A challenge for 6, 12, and 24 h compared with those of WT CD4+ T cells. Activation-induced apoptosis was also significantly increased in Glt25d2-/- CD4+ T cells after Con A challenge compared with WT CD4+ T cells. Lectin microarray hybridization showed that Glt25d2 knockout increased the binding activity of Narcissus pseudonarcissus lectin to CD4+ T cells but Amaranthus caudatus lectin-binding activity was lost during Con A challenge.

CONCLUSION:

The present results suggest that collagen glycosylation mediated by GLT25D2 may regulate a subset of CD4+ T cells and be involved in the pathogenesis of Con A-induced hepatitis.

• Authors: Xiaohua Hao, Ran Liu, Yifan Zhang, Yufeng Li, Qun He, Yubo Huang, Yu Jiang, Jiali Ma, Ping Li, Hongshan Wei
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 50 Issue 3 Pg. 1186-1200 ( 2018) ISSN: 1421-9778 [Electronic] Germany
• PMID: 30355948 (Publication Type: Journal Article)
• Copyright: © 2018 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• Antigens, CD
• Antigens, Differentiation, T-Lymphocyte
• CD69 antigen
• Chemokines
• Cytokines
• Interleukin-2 Receptor alpha Subunit
• Lectins
• Lectins, C-Type
• Concanavalin A
• Galactosyltransferases

Topics

• Animals
• Antigens, CD (metabolism)
• Antigens, Differentiation, T-Lymphocyte (metabolism)
• Apoptosis (drug effects)
• CD4-Positive T-Lymphocytes (cytology, drug effects, metabolism)
• Cell Proliferation (drug effects)
• Chemokines (blood)
• Concanavalin A (pharmacology)
• Cytokines (blood)
• Galactosyltransferases (deficiency, genetics)
• Hepatitis, Animal (etiology, immunology, pathology)
• Interleukin-2 Receptor alpha Subunit (metabolism)
• Lectins (metabolism)
• Lectins, C-Type (metabolism)
• Liver (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Spleen (metabolism)