# The Role of the Adenosine Receptor in Th Cell Development and Function

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $503,617

## Abstract

ABSTRACT/SUMMARY
 Immunological homeostasis reflects a balance between the host response and the antigenic environment.
In mucosal immunology, inflammatory bowel diseases (IBD), including ulcerative colitis or Crohn’s disease,
reflect a disruption in homeostasis with exaggerated host responses to the local microbiota in genetically
susceptible hosts. Our microbial communities are dynamic so regulatory Th cells induced in the periphery
(pTreg) are important to maintain a flexible homeostasis with these diverse organisms. Many factors modify the
metabolic balance that maintains homeostasis and Treg function. Relevant to this proposal, studies have
associated a disruption in adenosine metabolism with IBD in humans and in animal models. Adenosine is a
purine metabolite derived from ATP through its conversion to ADP and 5’AMP by CD39 while CD73 continues
the metabolism to adenosine. As the production of ATP from dead cells or bacteria is pro-inflammatory, its
catabolism to adenosine is one means to restrict inflammation. Adenosine has direct anti-inflammatory
properties mediated primarily through the A2A adenosine receptor (A2AAR) expressed by lymphocytes as well
as antigen presenting cells and innate lymphoid cells. Moreover, we present new findings suggesting that
adenosine shifts the energy metabolism in Th cells in order to confer its anti-inflammatory effects. Other data
show that the absence of adenosine initiates the expansion of pathogenic Th cells, a decrease in Treg, and
selects for microbiota that transmit susceptibility to colitis. The hypothesis for this study is that adenosine is
required to maintain immunological homeostasis in the digestive tract. More specifically, disrupting adenosine
production or responsiveness impacts lymphoid cell fate that subsequently changes bacterial colonization,
creates a dysbiosis and promotes inflammation. The broad objective of the project is to define the role of
purine metabolism on the control of immunological homeostasis in the gut as addressed in the following
interrelated Specific Aims:
 Aim 1: Identify how lymphoid-microbial homeostasis relies on adenosine.
 Aim 2: Determine how adenosine controls protective responses to microbiota
 Aim 3: Define the role of purine metabolism in controlling lymphoid cell fate. .
 The proposed experiments will explore novel aspects of immunological homeostasis. These studies will
have a positive impact on the basic understanding of lymphoid cell plasticity and provide new knowledge that
can be used to expedite the identification and development of therapeutic strategies for immune-mediated
diseases.

## Key facts

- **NIH application ID:** 9829518
- **Project number:** 5R01AI079145-09
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Peter B. Ernst
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $503,617
- **Award type:** 5
- **Project period:** 2017-12-06 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9829518

## Citation

> US National Institutes of Health, RePORTER application 9829518, The Role of the Adenosine Receptor in Th Cell Development and Function (5R01AI079145-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9829518. Licensed CC0.

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