# An autoimmune center of excellence for the study of IgG4-related disease

> **NIH NIH U19** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $336,000

## Abstract

PROJECT SUMMARY
This project focuses on the underlying basis of two autoimmune fibrotic disorders, IgG4-
related disease and systemic sclerosis. We will use multi-color multispectral imaging of
disease tissues, cell distance mapping as well as single-cell transcriptomics to
interrogate tissues from IgG4-related disease. In particular we wish to identify and
quantitate CD4+cytotoxic T cells and activated B cell subsets and better understand
whether they directly contribute to cell death in tissues and thus to fibrosis, or if they
primarily secrete fibrogenic products. We also want to understand the molecular basis by
which CD4+cytotoxic T cells differentiate. We will test two competing but mutually non-
exclusive hypotheses - one that CD4+T cells, with the help of activated B cells drive
tissue cell death as a prelude to fibrosis, and the other that the cytokines and enzymes
secreted by activated T cells and disease-related B cells are causal for fibrosis. We will
also examine the interactions between adaptive and innate immune cells in disease and
identify antigens that trigger clonally expanded B and T cells in patients. We will also
explore the possibility that somatic mutations in hematopoietic stem cells or in CD4+CTL
clones contribute to disease pathogenesis. We will also examine whether intestinal
microbial gene expression reveals differences between subsets of disease or explains
responsiveness to therapy. The possible contribution of microbial metabolites to immune
cell differentiation will be examined and microbial antigens that activate host T cells will
also be identified.

## Key facts

- **NIH application ID:** 10188397
- **Project number:** 5U19AI110495-08
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** SHIV Subramaniam PILLAI
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $336,000
- **Award type:** 5
- **Project period:** 2014-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10188397

## Citation

> US National Institutes of Health, RePORTER application 10188397, An autoimmune center of excellence for the study of IgG4-related disease (5U19AI110495-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10188397. Licensed CC0.

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