# Characterizing Innate Immune Dysregulation in Tonsils of Individuals with Down Syndrome

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $3,038,439

## Abstract

PROJECT ABSTRACT
People with Down syndrome (DS) are more likely to develop pulmonary infections compared to disomic
individuals. While the etiology of the infections in T21 individuals is almost certainly multifactorial, we have
begun examining the tonsils from T21 and D21 children undergoing tonsillectomy for obstructive sleep apnea.
Tonsils are considered secondary lymphoid tissues (SLTs) and within these tissues, unique tissue-resident cell
populations exist. Recent studies have demonstrated that SLTs are also the site of natural killer (NK) cell and
innate lymphoid cell (ILC) development. Our preliminary data show dramatic differences in T21 vs. D21
tonsils. For instance, we find lower numbers of hematopoietic (CD45+) cells in the tonsils of age matched T21
individuals. Likewise, there are higher bacterial loads in T21 (again, all tonsils were removed for obstructive
sleep apnea and not tonsillitis). We also note dramatic perturbations in the ratios of NK cells and ILCs, with
T21 individuals having higher proportions of NKs and fewer ILC3s. Given the role of ILC3s in mucosal
integrity, these findings may account for the elevations in bacterial loads. Lastly, we have identified a rare
population of cells, previously described mainly in murine models, as NKB cells which have characteristics of
both NK cells and B cells. In mice, these cells respond to bacterial challenge by producing cytokines that
activate NK cells. Over the course of three separate, but highly inter-related specific aims, we will address how
the triplication of the four interferon receptors (FNAR1, IFNAR2, IFNGR2 & IL-10RB, all present on
chromosome 21) may account for the above differences in T21 vs. D21 SLTs. As well, this data leads to a
model where excessive IFN signaling reduces ILC3 cell numbers, which in turn leads to a lack of mucosal
integrity and higher bacterial colonization which further drives immune activation, including the increase in the
proportion of the novel NKB population.

## Key facts

- **NIH application ID:** 10108932
- **Project number:** 1R01HL155691-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Michael R. Verneris
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $3,038,439
- **Award type:** 1
- **Project period:** 2020-09-18 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10108932

## Citation

> US National Institutes of Health, RePORTER application 10108932, Characterizing Innate Immune Dysregulation in Tonsils of Individuals with Down Syndrome (1R01HL155691-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10108932. Licensed CC0.

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