# Mechanisms of IL-23 receptor-mediated pathogenicity in CD4+ T cells

> **NIH NIH K08** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $168,848

## Abstract

Project Summary/Abstract
This proposal presents a five year research career development program focused on the study of the role of the
IL-23 receptor (IL-23R) on CD4+ T cells in cutaneous lupus erythematosus (CLE). The candidate is currently an
Instructor in Dermatology at Harvard Medical School in the Department of Dermatology at the Brigham and
Women's Hospital. The outlined proposal builds upon the candidate's previous research and clinical experience
in molecular and cellular immunology and cutaneous biology by leveraging the use of emerging genomic
technologies within Dr. Vijay Kuchroo's, his primary mentor's, laboratory. The proposed experiments and didactic
work will position the candidate with a unique set of cross disciplinary skills that will enable him to transition to
independence as a physician scientist in autoimmune cutaneous biology.
Cutaneous involvement is a major feature of systemic lupus erythematosus (SLE), a systemic autoimmune
disease affecting multiple organs, but can also occur in the absence of systemic disease. Cutaneous lupus
erythematosus (CLE) significantly impacts patients' quality of life, socioeconomic status, and can result in
permanent scarring and dyspigmentation. Therefore, more effective therapies are critically required. However,
our current understanding of CLE pathogenesis is limited, making the development of targeted therapies
difficult. As a consequence, patient care can be negatively impacted as optimal treatment regimens cannot
always be achieved. Therapies can improve the skin, systemic disease, both, or neither. Therefore, it is of critical
importance that a better understanding of the basic immunologic underpinnings of CLE pathogenesis be
achieved to meet this clinical need. This proposal aims to investigate the role of IL-23R expression on CD4+ T
cells in the development of CLE. The proposed project will directly address this vital question while overcoming
current limitations in the field. Aim 1 will examine the mechanisms by which the IL-23R confers pathogenicity to
CD4+ T cells. Aim 2 tests whether the IL-23R confers pathogenicity to CD4+ T cells, which can then drive
spontaneous skin inflammation in a mouse model of lupus erythematosus. Aim 3 leverages cutting edge genomic
technologies and analysis to identify novel, transcriptionally distinct, pathogenic CD4+ T lymphocytes in the CLE
lesional skin. Taken together, this project combines traditional molecular and cellular approaches with emerging
genomic technologies and analysis to address a critically unmet need in cutaneous autoimmune disease.

## Key facts

- **NIH application ID:** 10428485
- **Project number:** 5K08AR079007-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Allen Wayne Ho
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $168,848
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10428485

## Citation

> US National Institutes of Health, RePORTER application 10428485, Mechanisms of IL-23 receptor-mediated pathogenicity in CD4+ T cells (5K08AR079007-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10428485. Licensed CC0.

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