# Novel collagen V-reactive natural Th17 cells in hypoxic pulmonary hypertension

> **NIH NIH R56** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2020 · $378,750

## Abstract

Hypoxic pulmonary hypertension (PH) is a progressive and often fatal consequence of chronic lung
diseases, chronic exposure to high altitude and acute lung injury. We have demonstrated that TH17
cells, a pro-inflammatory T helper (TH) cell (CD4+) subset, are localized in the perivascular region of
pulmonary arteries. These cells contribute to CH-induced PH. However, whether immunity to self-
antigens contributes to disease progression is unknown. Type V collagen (col V) is normally
sequestered within the lung interstitium and therefore, hidden from the immune system. Hypoxia could
lead to exposure of col V and be a source of antigen. Col V cellular immunity contributes to TH17-
dependent obliterative bronchiolitis post-lung transplant, atherosclerosis and interstitial lung fibrosis.
However, it is unknown whether colV cellular immunity plays a role in the TH17 cell-dependent
perivascular inflammation that contributes to CH-induced PH and the mechanism of TH17 cells homing.
It is also unknown if this TH17 cells belong to the natural occurring (nTH17) subset. Therefore, we
propose the novel hypothesis that nTH17-mediated PH develops as a result of increased col V-reactive
nTH17 cells and reduced peripheral tolerance to col V. We also propose that this mechanism requires
nTH17 cell trafficking to the perivascular region under the guidance of C-C motif chemokine ligand 2
(CCL2)/C-C chemokine receptor type 2 (CCR2) signaling. We will pursue the following aims:
Specific Aim 1: To identify lung-associated self-antigens induced or exposed by CH. Hypothesis: Col V
is a lung-associated self-antigen uncovered by CH that triggers nTH17 cell-mediated perivascular
inflammation.
Specific Aim 2: To identify the mechanism of nTH17 cell homing to the perivascular region in response
to CH. Hypothesis: CCL2/CCR2 signaling drives nTH17 cell homing to the perivascular region in
response to CH.
Specific Aim 3: To determine the contribution of loss of peripheral tolerance to self-antigens in PH.
Hypothesis: A loss in the normal balance between col V-reactive nTH17 cells and nTregs due to nTreg
transition to an nTH17 phenotype contributes to the development of PH.
Completion of these studies will identify the self-antigens or neo-antigens exposed by CH, determine
triggers for nTH17 cell-homing to the pulmonary perivascular region, and the role of peripheral
tolerance in this pathway. This groundbreaking study will also facilitate the development of therapies
to selectively inhibit the generation of autoreactive T cells and their trafficking to the site of
inflammation without affecting the capacity of the host to mount a proper inflammatory response to
pathogens.

## Key facts

- **NIH application ID:** 10267902
- **Project number:** 1R56HL153065-01
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Laura V Gonzalez Bosc
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $378,750
- **Award type:** 1
- **Project period:** 2020-09-24 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10267902

## Citation

> US National Institutes of Health, RePORTER application 10267902, Novel collagen V-reactive natural Th17 cells in hypoxic pulmonary hypertension (1R56HL153065-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10267902. Licensed CC0.

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