# Control of lymphocyte homeostasis by iCD8a cells and osteopontin

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $355,500

## Abstract

SUMMARY
In this application we propose to investigate the biological features of innate CD8α cells (or iCD8α cells), a
novel lymphoid population present in the intestinal epithelium discovered by our group. A hallmark of this
population is the expression of CD8αα, lack of T and B cell receptors, and the production of
cytokines/chemokines that indicate an innate immune phenotype. iCD8α cells are a main source of
osteoponin in the intestinal epithelium, a cytokine known for its role in tissue remodeling but also for its
capacity to stimulate Th1 and Th17 immune responses. Interestingly, using a strain of mice lacking iCD8α
cells (E8I mice; E8I is an essential enhancer for CD8αα expression in IEL) we found that the levels of
-/-
osteopontin in the intestinal epithelium are decreased in comparison to wild type mice, and that E8I-/- mice
have a deficiency in NKp46+NK1.1+ IEL. These and other preliminary results have led to the hypothesis that
iCD8α cells, through production of factors such as osteopontin, promote the survival and
maintenance of IEL. In order to pursue this hypothesis, we propose the following complementary, yet
independent aims: Aim1. To determine the contribution of iCD8α cells and osteopontin to IEL
maintenance and survival. In this aim we will determine: a) the impact of iCD8α cells and osteopontin in
the survival and proliferation of different IEL subsets; b) the impact of iCD8α cells and osteopontin in the
immune environment of the intestines; and c) the role of osteopontin ligands in IEL homeostasis. Aim 2. To
define the role of iCD8α cells and osteopontin during intestinal inflammation. In this section we will
determine the role of iCD8α cells and osteopontin in three different disease models: a) intestinal
inflammation by anti-CD40 antibody treatment, b) Citrobacter rodentium infection, and c) inflammation
caused by adoptive transfer of effector T cells into immunodeficient mice. Aim 3. To determine the
mechanisms controlling IEL homeostasis by iCD8α cells. Our previous publication indicates that IL-12
provides stimulus for activation of iCD8α cells. In this section we will determine a) the impact of IL-12 in
activation of iCD8α cells, with implications on OPN secretion and IEL survival, and b) we will determine the
gene expression signature of IEL responding to iCD8α cell/OPN stimulation.

## Key facts

- **NIH application ID:** 10178005
- **Project number:** 5R01DK111671-05
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Danyvid Olivares-Villagomez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $355,500
- **Award type:** 5
- **Project period:** 2017-07-05 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10178005

## Citation

> US National Institutes of Health, RePORTER application 10178005, Control of lymphocyte homeostasis by iCD8a cells and osteopontin (5R01DK111671-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10178005. Licensed CC0.

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