# T helper cells in development of chronic inflammation and multimorbidity

> **NIH NIH R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2024 · $626,628

## Abstract

Multimorbidity, the coexistence of two or more chronic and often aging-related diseases, affects the majority of
older adults. Chronic inflammation has been implicated in multimorbidity and individual aging-related diseases
including cardiovascular disease, diabetes, cancer, Alzheimer’s disease, and osteoporosis. Anti-inflammatory
therapy targeting IL1β reduces risk for cardiovascular disease, but clinical benefits of modulating inflammation
remain controversial. Animal studies suggest that the infiltration of immune cells including T helper cells into
the arterial wall, adipose, and other tissues may be the central mechanism underlying chronic inflammation
and subsequent diseases. Most human studies, however, rely on inflammatory biomarkers such as IL6 and
CRP, which lack mechanistic specificity. The paucity of human studies directly characterizing the immune cells’
role in the inflammatory process is a major gap retarding the translation of animal-based mechanistic work. We
propose that T helper cells are an important contributor to both chronic inflammation and subsequent diseases
because of their regulating immune response of both adaptive and innate immune cells including activation of
monocytes/macrophages. This view is supported by our preliminary data from the Multi-Ethnic Study of
Atherosclerosis (MESA) which shows the associations of pro-inflammatory signatures of T helper cells with
multimorbidity, chronic inflammation, and inflammatory response of monocytes. While these microarray data
support the role of T helper cells in chronic inflammation and multimorbidity, large longitudinal studies are
needed to establish whether cellular features precede disease development. The proposed study will leverage
the unique resource of isolated human T helper cells in MESA (N=1,900). We hypothesize that cellular
features that coordinate the inflammatory response in peripheral T helper cells contribute to subsequent
chronic inflammation, inflammatory changes in peripheral monocytes, and multimorbidity. To test this
hypothesis, we will examine the following specific aims: 1) to examine whether omics profiles of T helper cells
predict 11-year changes in multimorbidity in 1,900 MESA participants, 2) to evaluate whether omics profiles of
T helper cells predict 6-year changes in omics profiles of monocytes and circulating pro-inflammatory
biomarkers in 1,900 individuals, and 3) To test effects of pharmacological modulation of T helper cells from
MESA participants on inflammatory responses. The proposed study will for the first time investigate the
longitudinal relationship between omics profiles of T helper cells and multimorbidity in humans. The results
from the proposed study will improve our understanding of inflammatory processes in humans, particularly their
cellular features, and accelerate the development of more precisely targeted anti-inflammatory interventions for
preventing multimorbidity.

## Key facts

- **NIH application ID:** 10904014
- **Project number:** 5R01AG078359-02
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** JINGZHONG DING
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $626,628
- **Award type:** 5
- **Project period:** 2023-08-15 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10904014

## Citation

> US National Institutes of Health, RePORTER application 10904014, T helper cells in development of chronic inflammation and multimorbidity (5R01AG078359-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10904014. Licensed CC0.

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