# Regulation of Th2 differentiation by skin-resident dendritic cells

> **NIH NIH R01** · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2024 · $462,795

## Abstract

Project Summary
T helper type 2 (Th2) cells play a crucial role in allergies, humoral immunity and host protection against
parasitic infections, but our understanding of the mechanism of their differentiation remains incomplete. Upon
encountering a cognate antigen presented by dendritic cells (DCs), naive CD4T cells make a fate decision to
become one of the effector cell types such as Th1, Th2, and Th17 cells. However, unlike their differentiation
into Th1 or Th17 cells, in which IL-12 and IL-23 play a crucial role, respectively, the DC-derived fate
instruction signal universally required for Th2 differentiation has not been identified.
CD301b (Mgl2) and its human homolog CLEC10A are selectively expressed by a major subset of type 2
conventional DCs in the dermis and other peripheral organs. We previously developed mouse models in
which CD301b+ DCs are depleted, enriched or genetically manipulated and demonstrated that CD301b+DCs
are both necessary and sufficient for the Th2 cell differentiation upon exposure to a protease allergen papain
in the skin as well as after infection with a hookworm Nippostrongylus brasiliensis. Interestingly, the depletion
of CD301b+DCs results in a shift of the effector CD4T cell phonotype from Th2 to Th1 and Th17 phenotype,
suggesting that CD301b+ DCs regulate the effector cell fate at the clonal level. The molecular mechanism for
the Th2 fate instruction by CD301b+DCs still remains unclear, but our data indicate the requirement of
cognate interactions between CD301b+DCs and antigen-specific CD4T cells. Thus, we hypothesize that
CD301b+ DCs imprint the Th2 fate on CD4T cells mainly through a contact-dependent, rather than soluble,
mechanisms.
In this application, we aim to address the following two questions by vigorously characterizing the CD4T cell
differentiation kinetics in our unique mouse models: (1) What is the CD4T cell-intrinsic, Th2-skewing signal(s)
imprinted by CD301b+ DCs?; and (2) How do CD301b+ DCs instruct antigen-specific CD4T cells to become
Th2 cells? Answering these questions will deepen our basic understanding of the in vivo mechanism of the
initiation of a Th2 response and help us to develop a unified model that comprehensively explains the role of
DC subsets in CD4T cell differentiation. Understanding such mechanism would help us to improve our
strategies for treating allergic diseases and developing effective vaccines for infectious diseases.

## Key facts

- **NIH application ID:** 10857213
- **Project number:** 5R01AI132576-07
- **Recipient organization:** RUTGERS BIOMEDICAL AND HEALTH SCIENCES
- **Principal Investigator:** YOSUKE KUMAMOTO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $462,795
- **Award type:** 5
- **Project period:** 2017-08-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10857213

## Citation

> US National Institutes of Health, RePORTER application 10857213, Regulation of Th2 differentiation by skin-resident dendritic cells (5R01AI132576-07). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10857213. Licensed CC0.

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