# A Cellular Pilot of Human T Lymphocytes

> **NIH NIH R21** · UNIVERSITY OF PENNSYLVANIA · 2020 · $243,000

## Abstract

The overall objective of this R21 research project is to elucidate a new pathogenic mechanism
involved in multiple sclerosis (MS) so that new therapies can be developed to treat the disease.
While MS is triggered by a number of genetic and environmental factors, a common pathogenic
mechanism is the infiltration of the central nervous system (CNS) by circulating leukocytes. How
leukocytes migrate into CNS is not well understood. It is believed that an internal cellular pilot,
akin to a ship’s maritime pilot, guides leukocyte migration into nervous tissue; but the nature of
this cellular pilot remains poorly defined. This R21 application is inspired by our recent discovery
that murine leukocytes deficient in the TIPE (tumor necrosis factor-a-induced protein 8-like) family
of proteins are defective in directed migration: they are unable to migrate toward chemoattractants
or into nervous tissue to cause encephalomyelitis despite their normal activation status. TIPE
proteins are risk factors for both multiple sclerosis and plantar fasciitis as revealed from recent
genome-wide association studies (GWAS), and their expression is dysregulated in a number of
human diseases including autoimmune diseases. We initially cloned the TIPE2 gene from the
spinal cord of mice with experimental autoimmune encephalomyelitis (EAE) and found that it was
preferentially expressed by leukocytes. We then generated mice deficient in TIPE2 and found that
they were significantly resistant to EAE. Unexpectedly, TIPE-deficient T cells have no defect in
activation, but are severely compromised in their ability to migrate into nervous tissue and to
induce EAE. In this proposal, we will test the hypotheses that (i) TIPE proteins control the
migration of human T cells, and (ii) TIPE family is the pilot of human T cells.

## Key facts

- **NIH application ID:** 9985424
- **Project number:** 1R21AI149771-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Youhai H Chen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $243,000
- **Award type:** 1
- **Project period:** 2020-01-24 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985424

## Citation

> US National Institutes of Health, RePORTER application 9985424, A Cellular Pilot of Human T Lymphocytes (1R21AI149771-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9985424. Licensed CC0.

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