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The role of Blimp-1 transcriptional regulator in adipose-resident Tregs

Beppu, Lisa (2021) The role of Blimp-1 transcriptional regulator in adipose-resident Tregs. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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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.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Beppu, Lisalisa.beppu@pitt.edulib54
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorD'Cruz,
Committee ChairPoholek,
Committee MemberO'Doherty,
Committee MemberDelgoffe,
Committee MemberPiganelli,
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


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