# Mechanisms of Interferon-Lambda Programming at the Innate-Adaptive Immune Interface for Protection Against Virus Infection

> **NIH NIH K22** · OHIO STATE UNIVERSITY · 2022 · $107,143

## Abstract

Project Summary. The innate-adaptive immune interface represents the site of action where components of
both innate and adaptive immunity cross-engage each other to program the effector actions of the adaptive
immune response. The actions of the innate-adaptive immune interface are considered essential for
establishing protective immunity and immune memory against virus infection. Type III interferon (IFN-λ) is a
cytokine that functions at the innate-adaptive immune interface and is critical for mediating innate immune
protection at mucosal barriers. IFN-λ provides therapeutic benefit against Influenza A virus (IAV) infection,
however how it operates within the innate-adaptive interface is not defined. We have utilized a murine model of
IAV infection to study the contribution of IFN-λ in regulation of immunity at the innate-adaptive interface during
respiratory virus infection. Our studies show Ifnlr1-/- mice have blunted effector CD8+ T cell responses
compared to WT mice and exhibit reduced survival upon heterosubtypic IAV re-challenge. Analysis of dendritic
cells (DCs) reveals that IFN-λ signaling directs CD103+ DC migration and function to develop optimal anti-viral
CD8+ T cell responses. Further, preliminary bioinformatic analysis suggests IFN-λ is essential for control of an
Il10 immunoregulatory network in DCs during IAV infection. Our observations reveal that IFN-λ bridges innate
and adaptive immunity to direct DCs to program effective T cell immunity against IAV. We hypothesize IFN-λ
signaling in DC regulates an IL-10 program critical for development of effective T cell memory for lasting
immunity against IAV. Thus, the studies in this proposal aim to: 1) determine the contribution of IFN-λ to
generation of memory CD4+ and CD8+ T cell responses and 2) elucidate IFN-λ regulation of IL-10 in
programming DC functions. Results from these studies will define the role of IFN-λ at the innate-adaptive
immune interface in programming effective immunity against IAV infection and inform IFN-λ-based vaccine and
immune therapy strategies to prevent and limit infection.
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## Key facts

- **NIH application ID:** 10368914
- **Project number:** 5K22AI146141-02
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Emily Ann Hemann
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $107,143
- **Award type:** 5
- **Project period:** 2021-03-09 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10368914

## Citation

> US National Institutes of Health, RePORTER application 10368914, Mechanisms of Interferon-Lambda Programming at the Innate-Adaptive Immune Interface for Protection Against Virus Infection (5K22AI146141-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10368914. Licensed CC0.

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