# Crosstalk between MAIT cells and the microbiota

> **NIH NIH K22** · SCRIPPS RESEARCH INSTITUTE, THE · 2022 · $108,000

## Abstract

Project Summary/Abstract
Career Goals: My overarching career goal is to become an independent investigator at an academic institution
where I study how the microbiota impacts the development and function of the immune system, ultimately
translating my findings into novel treatments. I also aspire to become an inspirational teacher and mentor.
Career Development: In addition to meeting weekly with Dr. Belkaid, I will discuss my progress with my mentors
at least once every 6 months for the duration of the award. The NIH has numerous training resources which will
be pivotal to my development, including courses and workshops. I will enhance my ability to analyze
computational datasets by participating in bioinformatics courses, enroll in courses to improve my teaching and
mentoring, and attend seminars on the transition to independence and management. I will further develop my
communication skills prior to the K22 award by authoring 2 manuscripts and presenting at least 8 times at
seminars and conferences.
Environment: The NIH Intramural Research Program has more than 1,200 PIs conducting basic, translational,
and clinical research, a plethora of core facilities, and resources for the career development of postdocs. The
NIAID Microbiome Program has a gnotobiotic animal facility and a sequencing facility that also provides
bioinformatics analysis. There are numerous seminar series featuring external faculty and others that allow
trainees to present their research. Prior to the K22 award, I will work in the laboratory of Dr. Belkaid, which is a
BSL-2 research space and is adequately equipped to conduct the proposed experiments.
Research: Skin infections are the 4th most prevalent cause of disease globally, indicating that cutaneous
diseases are a major health concern. In addition to inhibiting colonization by pathogens through competition and
the induction of immune responses, the microbiota promotes immune homeostasis via the release of microbial
products. Human skin harbors mucosal-associated invariant T (MAIT) cells, which rapidly produce either Th1-
or Th17-associated cytokines in response to microbial vitamin B2 derivatives presented by the MHC-Ib molecule,
MR1. We have recently found that IL-17A+ MAIT cells are highly abundant in murine skin and depend on the
microbiota. However, the mechanism by which commensals promote MAIT cell development remains unknown.
To address this, I will identify microbes that induce MAIT cell development and elucidate the mechanism using
an Mr1f/f conditional knockout and other murine models. Administration of these commensals to mice challenged
with cutaneous pathogens will establish whether the microbiota can enhance the contribution of MAIT cells to
skin immunity, which could have clinical applications due to the high frequency of cutaneous MAIT cells.

## Key facts

- **NIH application ID:** 10404907
- **Project number:** 5K22AI146217-02
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Michael George Constantinides
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $108,000
- **Award type:** 5
- **Project period:** 2021-05-14 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10404907

## Citation

> US National Institutes of Health, RePORTER application 10404907, Crosstalk between MAIT cells and the microbiota (5K22AI146217-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10404907. Licensed CC0.

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