# Role of Blimp1 (Prdm1) in lung immune responses and tolerance

> **NIH NIH R01** · CEDARS-SINAI MEDICAL CENTER · 2020 · $505,205

## Abstract

PROJECT SUMMARY
The lungs and upper airways are mucosal surfaces that are regularly exposed to the external
environment. Like other mucosal surfaces in the body (e.g. intestines, and female reproductive
tract) proper functioning of the lungs and airways requires avoidance of chronic inflammation. The
pathways underlying immune homeostasis and tolerance to exogenous stimuli at mucosal
surfaces are complex, diverse and poorly understood. During the last funding period, our studies
have identified different molecular pathways regulated by the transcription factor Blimp1 (encoded
by the Prdm1 gene) that promote immune homeostasis in the intestinal mucosa and potentially
other mucosal surfaces such as the lungs. We have discovered that Blimp1 is specifically
expressed in a subset of regulatory T lymphocytes in the intestines and that expression of Blimp1
in these cells is required to maintain their regulatory properties and prevent acquisition of
inflammatory properties. In addition, our studies revealed that lack of Blimp1 in T cells is
associated with increased expression of the inflammatory cytokine IL9 and worsened airway
inflammation. During the funding period of the award we generated a new knock-in Blimp1
reporter mouse that allowed visualization of Blimp1 expression in hematopoietic cells at the
steady state in different tissues, including environmental surfaces. The new finding that led us to
form the basis for this renewal application was the observation that Blimp1 is constitutively
expressed in lung resident alveolar macrophages at higher levels than the observed in other
myeloid cells in the lung and in other tissues. More importantly, we found that deletion of Blimp1
in macrophages in mice compromised the response against the pneumoniae-causing bacteria
Streptococcus pneumoniae, leading to exacerbated inflammatory responses, worsened lung
tissue damage and increased bacterial burden. Moreover, we identified MHC class II and the
regulatory molecules CD200R1 and IL10 as putative targets of Blimp1 in lung macrophages.
Together, these observations led to our hypothesis that Blimp1 functions as critical regulator to
maintain immune homeostasis in the lungs by restraining inflammatory activity of both lymphoid
and myeloid cells. In this proposal we will define the cellular and molecular mechanisms by which
Blimp1 promote immune homeostasis in the lung. We anticipate that achievement of the goals of
this application will uncover novel mechanisms underlying control of immune response and
tolerance in the lungs and will inform the development of new therapeutic approaches to treat
chronic lung inflammatory conditions.

## Key facts

- **NIH application ID:** 10053203
- **Project number:** 2R01AI103542-06A1
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Gislaine A Martins
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $505,205
- **Award type:** 2
- **Project period:** 2013-05-29 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10053203

## Citation

> US National Institutes of Health, RePORTER application 10053203, Role of Blimp1 (Prdm1) in lung immune responses and tolerance (2R01AI103542-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10053203. Licensed CC0.

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