# Elucidating microbial and host mechanisms supporting early life immune imprinting by skin monocytes

> **NIH NIH R00** · OHIO STATE UNIVERSITY · 2024 · $249,000

## Abstract

PROJECT SUMMARY/ABSTRACT:
 Early life interactions between commensal microbes and the developing immune system have formative
effects on human health and susceptibility to chronic inflammatory disease. Previous studies from the host lab
and other groups have demonstrated that our microbial symbionts can tune skin-resident T cell function,
especially during the neonatal window. However, comparatively little is known about how commensals influence
cutaneous myeloid immunity in early life. Dr. Dhariwala has found that commensal microbes influence the
composition and function of the myeloid compartment in neonatal skin. Specifically, commensal microbes drive
the accumulation of a population of Ly6ChiMHC-IIlo inflammatory monocytes in neonatal skin. These cells have
traditionally been studied as primary mediators of inflammation in response to infection or for their ability to fill
vacant tissue myeloid niches. However, Dr. Dhariwala’s preliminary studies demonstrate a previously unexplored
regulatory immune imprinting role for neonatal skin monocytes. To dissect the molecular mechanisms that
underpin this phenomenon, we will employ a combination of transgenic mouse models, high throughput assays
like mass cytometry and single cell RNA sequencing along with novel ex vivo translational tools. Studies
proposed in this application will (Aim 1) Dissect the mechanism(s) by which commensal microbes influence
monocyte recruitment and function in neonatal skin, (Aim 2) Elucidate the mechanism(s) by which neonatal
monocytes contribute to skin immune homeostasis and (Aim 3) Functionally elucidate the role of neonatal
monocytes in human skin. Results from this cross-disciplinary approach will benefit our understanding of early
immune development and lay the groundwork for next generation therapies for chronic inflammatory diseases.
 The proposed research and training plan will build on Dr. Dhariwala’s strengths in the fields of microbiology,
immunology and translational science. Leveraging tools he has established in the host lab, such as mass
cytometry, ex vivo functional assays in human skin and manipulation of skin-resident myeloid cell populations in
murine models, along with studies like metabolomics proposed in this application will not only elevate the project
but also advance his training. His scientific and career progress will be well supported by a strong mentorship
team including Drs. Tiffany Scharschmidt, Clifford Lowell, Michael Rosenblum and Peter Turnbaugh.
Additionally, through presentations at local and international conferences along with formal and informal training
at UCSF Dr. Dhariwala will advance his transition to independence. Promising preliminary data, a strong training
plan and an excellent training environment will allow Dr. Dhariwala to carve out a niche for himself and establish
an independent research program studying the influence of commensal microbes on myeloid immune
development in neonatal barrier tissues.

## Key facts

- **NIH application ID:** 10897434
- **Project number:** 4R00AR079554-03
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Miqdad Onali Dhariwala
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2024-06-21 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10897434

## Citation

> US National Institutes of Health, RePORTER application 10897434, Elucidating microbial and host mechanisms supporting early life immune imprinting by skin monocytes (4R00AR079554-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10897434. Licensed CC0.

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