# Type 1-2 immune cross-regulation in the lung

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $45,909

## Abstract

Project Summary
Respiratory viral infections are a prevalent and ongoing threat to global health, as evidenced by seasonal
Influenza A infections and the SARS-CoV-2 pandemic. Notably, the association between allergy and asthma
and the severity of respiratory viral illness has been long observed but poorly understood. Group 2 innate
lymphoid cells (ILC2s) and the adaptive counterpart Type 2 CD4 helper cells (Th2) have been extensively
investigated for their role in allergic inflammation. Our group has described the localization of these type 2
lymphocytes (T2L) in non-lymphoid tissues, such as the lung, at rest and under allergic and mixed type 1-2
inflammation, observing localization near large airways and vessels at rest and expansion to the tissue
parenchyma with allergic inflammation. Interestingly, in mixed type 1-2 inflammation, T2L parenchymal
distribution is restricted due to Interferon gamma (IFNγ) signaling on T2L. My preliminary data demonstrates that
IFNγ-mediated restriction also occurs following viral respiratory infection with Influenza A virus (IAV, PR8) and
impacts mouse body weight and lung function. In parallel, I have demonstrated that loss IFNα/β signaling on
T2Ls increases body weight loss and impairs lung function in IAV, potentially through a distinct mechanism.
These data suggest that IFN-mediated restriction of T2L and T2L topography is critical for appropriate viral
clearance and/or tissue repair in viral respiratory infection. Mechanisms of IFN-mediated restriction of T2L have
been explored by many groups, including ours, however how this restriction of topography and counter-regulation
of T1 immunity by T2L dictate the immune response to viral infection remains elusive. I hypothesize that IFN
signaling regulates the topography and function of lung T2Ls in pulmonary viral infections. This proposal will
define the topography of T1-T2 cross-regulation in the setting of pulmonary viral infection (Aim 1) and evaluate
mechanism of interferon mediated restriction of type 2 lymphocytes (Aim 2). Completion of these aims will
elucidate the role of canonical type 1 and type 2 cytokines in mediating tissue resident lymphocyte function in
complex inflammation, providing novel mechanistic insight into how topography dictates immunity. Completion
of this study provides a foundation for the development of precision therapeutics to selectively regulate lung
resident lymphocytes subsets to impact the outcome of diverse lung diseases.

## Key facts

- **NIH application ID:** 10996003
- **Project number:** 1F31HL172636-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Sofia Caryotakis
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $45,909
- **Award type:** 1
- **Project period:** 2024-09-13 → 2026-09-12

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10996003

## Citation

> US National Institutes of Health, RePORTER application 10996003, Type 1-2 immune cross-regulation in the lung (1F31HL172636-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10996003. Licensed CC0.

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