# A clinical trial for psoriasis with novel single-cell genomic techniques to understand regulatory immunity behind long-term disease remission off drug induced by short-term IL-23 inhibition

> **NIH NIH K23** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2023 · $168,948

## Abstract

Although highly effective, biologics targeting IL-23/Th17 axis should be continuously injected to
suppress recurrence of psoriasis. My long-term goal is to cure psoriasis without recurrence guided by
personal immune tolerance. The overall objectives in this application are to (i) identify regulatory immune
cell interactions induced by anti-IL-23p19 antibody administration in the skin of patients whose psoriasis
is cleared without recurrence and (ii) develop pre-treatment predictive models for psoriasis patients that
anticipate disease recurrence after short-term anti-IL-23p19 antibody injection. The central hypothesis is
that IL-23p19 inhibition promotes regulatory immune cells in psoriasis patients whose disease is cleared
without recurrence, and their pre-treatment single-cell immune signatures are different from those of patients
whose disease recurs. The rationale for this project is that molecular evidence of immune tolerance
induction by IL-23p19 inhibition in human skin is likely to offer a strong clinical framework whereby new
strategies to prevent recurrence of chronic inflammatory diseases can be developed. The central hypothesis
will be tested by pursuing two specific aims: 1) Testing the hypothesis that regulatory immune cell
interactions are promoted by short-term anti-IL-23p19 antibody administration in the skin of psoriasis patients
whose disease becomes clear without recurrence; and 2) Developing predictive models with pretreatment
skin biopsy single-cell genomic data that anticipate long-term disease clearance off drug after
short-term anti-IL-23p19 antibody administration. To achieve the specific aims, we have recently developed
two innovative complementary single-cell approaches to obtain gene expression profiles of heterogeneous
immune cells from psoriasis and control skin without enzyme digestion. The first single-cell experimental
approach is microfluidic partitioning of emigrating cells from human skin after 48-hour incubation
in culture medium without enzyme digestion, which empowers single-cell transcriptomic profiling of
heterogeneous immune cells and keratinocytes in different layers of epidermis under ex vivo condition.
The second single-cell experimental approach is Combinatorial indexing RNA sequencing, developed by
the co-mentor of the proposal, which enables co-profiling transcriptome and single-cell chromatin accessibility.
At the completion of the proposed research, our expected outcomes are to have novel single-cell
genomic techniques to study immune cell interactions in human skin, defined single-cell gene signatures
of regulatory immune cells that are promoted by anti-IL-23p19 antibody administration in psoriasis skin,
and the ability to elucidate how pathologic immunity is suppressed at the single-cell level by highly effective
biologics. We also expect to have pre-treatment biomarkers that can predict long-term disease clearance
off drugs after short-term anti-IL-23p19 antibody administration.

## Key facts

- **NIH application ID:** 10685945
- **Project number:** 5K23AR080043-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Jaehwan Kim
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $168,948
- **Award type:** 5
- **Project period:** 2022-08-18 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10685945

## Citation

> US National Institutes of Health, RePORTER application 10685945, A clinical trial for psoriasis with novel single-cell genomic techniques to understand regulatory immunity behind long-term disease remission off drug induced by short-term IL-23 inhibition (5K23AR080043-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10685945. Licensed CC0.

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