SR-BI (Scavenger Receptor Class B Type 1) is critical in maintaining normal T-Cell development and enhancing thymic regeneration

Zhong Zheng, Junting Ai, Ling Guo, Xiang Ye, Subbarao Bondada, Deborah Howatt, Alan Daugherty, Xiang An Li

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Objective-Continuous T-cell production from thymus is essential in replenishing naïve T-cell pool and maintaining optimal T-cell functions. However, the underlying mechanisms regulating the T-cell development in thymus remains largely unknown. Approach and Results-We identified SR-BI (scavenger receptor class B type 1), an HDL (high-density lipoprotein) receptor, as a novel modulator in T-cell development. We found that SR-BI deficiency in mice led to reduced thymus size and decreased T-cell production, which was accompanied by narrowed peripheral naïve T-cell pool. Further investigation revealed that SR-BI deficiency impaired progenitor thymic homing, causing a dramatic reduction in the percentage of earliest thymic progenitors, but did not affect other downstream T-cell developmental steps inside the thymus. As a result of the impaired progenitor thymic homing, SR-BI-deficient mice displayed delayed thymic regeneration postirradiation. Using a variety of experimental approaches, we revealed that the impaired T-cell development in SR-BI-deficient mice was not caused by hematopoietic SR-BI deficiency or SR-BI deficiency-induced hypercholesterolemia, but mainly attributed to the SR-BI deficiency in adrenal glands, as adrenal-specific SR-BI-deficient mice exhibited similar defects in T-cell development and thymic regeneration with SR-BI-deficient mice. Conclusions-This study demonstrates that SR-BI deficiency impaired T-cell development and delayed thymic regeneration by affecting progenitor thymic homing in mice, elucidating a previously unrecognized link between SR-BI and adaptive immunity.

Original languageEnglish
Pages (from-to)2706-2717
Number of pages12
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume38
Issue number11
DOIs
StatePublished - 2018

Bibliographical note

Funding Information:
This study was supported by Grants R01GM113832 and R01GM121796 (to Dr Li) from the National Institute of General Medical Sciences (NIGMS)/National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIGMS or NIH.

Publisher Copyright:
© 2018 American Heart Association, Inc.

Keywords

  • Adrenal glands
  • Bone marrow cells
  • Bone marrow transplantation
  • Lymph nodes
  • Regeneration

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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