# A Prospective Study of T cell Immune-phenotype and Disease Outcome in Pulmonary Sarcoidosis

> **NIH NIH R01** · NATIONAL JEWISH HEALTH · 2021 · $992,527

## Abstract

PROJECT SUMMARY/ABSTRACT:
Sarcoidosis is a granulomatous disease of unknown etiology that affects the lungs in 90% of patients resulting
in significant morbidity and mortality. The disease has variable outcomes including persistent and/or
progressive and remitting disease, and there are no reliable or validated clinical tools available to predict these
outcomes. The goal of this study is it investigate changes in bronchoalveolar lavage (BAL) CD4+ T cell
phenotype and specific T cell lineage gene expression prospectively to understand the role of Th17.1 and Treg
cells with disease course. We will expand upon our novel findings that the most prevalent T effector cell in
sarcoidosis lung lavage are Th17.1 cells, capable of significant interferonγ (IFNγ) production (and may be a
source of additional mediators yet undefined). We also found that the abundance of Th17.1 cells were
inversely proportional to Treg cells, so that the highest frequencies of Th17.1 and the lowest frequencies of
Treg cells were found in patients with advanced disease. Our hypothesis is that the dynamic relationship of
multiple T cell effector lineages (Th1, Th17, Th17.1, Treg cells) affects the variable pathobiology and outcomes
in sarcoidosis. We hypothesize that sarcoidosis subjects with remitting disease have a decrease in BAL Th17.1
cells and increase in Treg cells over time. This is accompanied by dynamic changes in the transcriptional
signatures of the T cell lineages, which regulate their activity and plasticity. Using a longitudinal bronchoscopy
study design that has not been undertaken in sarcoidosis, we will prospectively enroll recently diagnosed
sarcoidosis subjects and sample BAL cells at two time-points to address our aims. Aim 1 will examine T cell
lineage diversity changes during sarcoidosis pathogenesis longitudinally in subjects with progressive vs.
remitting disease. In paired lung and blood samples, we will use multi-parameter flow cytometry analysis to
compare the frequencies of Th1, Th17, Th17.1, and Treg cells with clinical course (PFTs, chest x-ray, organ
involvement). In Aim 2, we will analyze alterations of T cell lineage activity during sarcoidosis pathogenesis via
genome wide transcriptional profiles of isolated Treg, Th17, Th17.1 and Th1 cells using low-input RNA-
sequencing. Flow sorted lung T cell populations will be used for low-input RNA-seq to compare longitudinal
changes to transcriptional signatures between T lineages cells with clinical course. Next, paired total lung and
blood RNA-seq analysis will be compared to identify overlapping signatures, which correlate with disease
outcomes. In aim 3, we will construct computational tools from T cell lineage diversity and gene expression
data to define and/or predict sarcoidosis endotypes using bioinformatic deconvolution and biostatistical
methods. The coupling of clinical, genomic and bioinformatic analysis will identify cellular and transcriptional
patterns that can be used to define novel sarc...

## Key facts

- **NIH application ID:** 10129990
- **Project number:** 5R01HL136681-04
- **Recipient organization:** NATIONAL JEWISH HEALTH
- **Principal Investigator:** NABEEL HAMZEH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $992,527
- **Award type:** 5
- **Project period:** 2018-04-15 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129990

## Citation

> US National Institutes of Health, RePORTER application 10129990, A Prospective Study of T cell Immune-phenotype and Disease Outcome in Pulmonary Sarcoidosis (5R01HL136681-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10129990. Licensed CC0.

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