Beppu, Lisa
(2021)
The role of Blimp-1 transcriptional regulator in adipose-resident Tregs.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Adipose-resident regulatory T cells are protective against local inflammation, and are believed to play a critical role in preserving insulin sensitivity and glucose tolerance. Although their basic markers and roles have been studied, less is known about the transcriptional machinery regulating their differentiation and function. B lymphocyte-induced maturation protein-1 (Blimp-1) is a transcriptional regulator known to be involved in development, polarization, and maintenance of various immune cells including CD4+ T cells. Using Blimp-1 reporter mice, we discovered that Blimp-1 is constitutively expressed in a subset of visceral adipose tissue (VAT) Tregs, and that Blimp-1+ VAT Tregs are phenotypically distinct from their Blimp-1- counterparts. We also found that Treg-specific Blimp-1 deletion led to reduced ST2+ KLRG1+, IL-10-producing VAT and inguinal adipose tissue (IAT) Tregs. Surprisingly, during diet-induced obesity, Blimp-1 Treg deficient mice gained less weight, had reduced body fat percentage, and exhibited improved insulin sensitivity compared to wild-type mice. Furthermore, this was accompanied by white adipocyte beiging. It has previously been shown that IL-10 can directly induce thermogenesis. Therefore, we repeated these experiments utilizing mice with Treg-specific deletion of IL-10 and found that they phenocopied the Blimp-1 Treg deficient mice. In summary, these findings reveal that Treg-adipocyte cross-talk can occur via a Blimp-1/IL-10 axis, and that the absence of Blimp-1+ Tregs increases white adipose tissue beiging and is metabolically protective against diet induced obesity.
Share
| Citation/Export: |
|
| Social Networking: |
|
Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
25 May 2021 |
| Date Type: |
Publication |
| Defense Date: |
15 April 2021 |
| Approval Date: |
25 May 2021 |
| Submission Date: |
10 May 2021 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
122 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Immunology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Adipose Tregs Obesity Blimp-1 Insulin resistance Cytokines IL-10 T cells Immunology Metabolism |
| Date Deposited: |
26 May 2021 03:05 |
| Last Modified: |
26 May 2021 03:05 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/41059 |
Metrics
Monthly Views for the past 3 years
Plum Analytics
Actions (login required)
 |
View Item |
![[feed]](/images/feed-icon-32x32.png){kind=icon}