# MHC-II deficient Langerhans cells with compensatory Tc17 plasticity in oral candidiasis

> **NIH NIH R21** · UNIVERSITY OF MINNESOTA · 2021 · $193,750

## Abstract

7. PROJECT SUMMARY / ABSTRACT
Oropharyngeal candidiasis can evolve into serious systemic infections with high morbidity and mortality rates in
post-surgical and immunocompromised patients. A thorough understanding of its immunopathogenesis is
critical to improve therapies that mitigate or prevents this disease. It is known that IL-17A provided by innate
and CD4-dependent adaptive immune responses is key to controlling Candida albicans (CA) invasion and
spread. What remains unknown is the role played by mucosal antigen presenting cells, in particular
Langerhans cells (LCs), on the development of compensatory IL-17A-producing CD8+ T cell populations
(Tc17) that are potentially protective against oral candidiasis. At homeostasis, lack of LCs or MHC-II
presentation on LC, expands the Tc17 population. Our long-range goal is to identify and characterize the
response to opportunistic microorganisms by components of the local immune that ultimately protect
individuals from diseases at oral mucosal surfaces. We have preliminary data that suggests that absence of
LCs and MHC-II presentation on LCs results in the secondary clonal expansion of Tc17, Tc1 and Treg cells at
homeostasis. Our current objectives are to determine how LCs control the numbers of mucosal Tc17 cells in
an MHC-II dependent manner and the extent of protection against CA when Tc17 are present. We
hypothesize that intraepithelial LCs regulate the numbers of Tc17 as a compensatory source of IL-17A and a
reservoir of IFN--producing Tc1 contributing to an efficient barrier against chronic CA infection. To test our
hypothesis, we will first determine if migration to lymph nodes is required for LCs to induce MHC-II-dependent
inhibition of oral Tc17. Second, determine if IL-6/STAT3 or TGF- are required to drive Tc17 persistence and
plasticity to Tc1 in the oral mucosa in vivo. To the best of our knowledge, we are the first group to define
MHC-II presentation on LCs as key factor in Tc17 expansion in the oral mucosa. We optimized interstitial
leukocytes sorting, enumeration and phenotype assessment from the oral mucosa excluding blood or nasal-
associated lymphoid tissues. Critically, we can unequivocally and permanently mark the phenotype and
developmental fate of IL-17A-expressing CA-specific CD3+ T cells assessing their phenotypic plasticity. Our
strategy employs genetic crossing of reporter- and silencing- murine strains. We can use MHC-I and MHC-II
tetramers capable of uniquely recognizing CD8+ and CD4+ T cells specific for an "epitope-tagged” CA strain.
We expect to determine the role of LCs as regulators of the developmental re-programming CA-specific Tc17
to Tc1 cells either in the oral mucosa or cervical lymph nodes. With a deeper understanding of the
mechanisms initiating oral candidiasis comes opportunities through therapeutic interventions to manipulate key
steps and mitigate or prevent systemic candidiasis.

## Key facts

- **NIH application ID:** 10194461
- **Project number:** 5R21DE029289-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** MASSIMO COSTALONGA
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $193,750
- **Award type:** 5
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10194461

## Citation

> US National Institutes of Health, RePORTER application 10194461, MHC-II deficient Langerhans cells with compensatory Tc17 plasticity in oral candidiasis (5R21DE029289-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10194461. Licensed CC0.

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