# Migration and function of cutaneous B cells

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2020 · $312,000

## Abstract

SUMMARY
The skin is a critical barrier organ and the frequent target of immune-mediated pathologies, such as psoriasis.
Despite a newly identified key role of B cells in pro-and anti-inflammatory cutaneous responses, little is known
about skin-associated B cells. We newly discovered that IL-10+ regulatory B cells (Bregs) with known potential
to suppress T cell-driven skin inflammation preferentially migrate into the inflamed skin of mice. We also
identified IL-10+ Bregs in human skin, validating human relevance of our findings in mice. Our studies show
that Breg trafficking into skin is independent of canonical skin-homing receptors and instead requires α4β1-
integrin, which was constitutively expressed in an activated state on Bregs. The data suggest that Bregs are
efficient skin-targeting cells and point to a so far unexplored anti-inflammatory pathway that may translate into
novel therapeutic approaches for inflammatory skin diseases. We hypothesize that skin Bregs fill a
specialized niche in the regulation of skin inflammation and that they can be targeted through their
migration. We also propose that impaired Breg recruitment into skin exacerbates skin inflammation.
Human psoriasis is associated with a dearth of cutaneous IL-10 and clinically responsive to IL-10 therapy. B
cell depletion induces psoriasis in some individuals, supporting a protective role of B cells in this disease.
Therefore, psoriasiform inflammation is likely affected by reduced recruitment of IL-10+ Bregs into skin and a
main focus of our studies. Under Aim 1 we will reveal the conditions that drive Breg accumulation in skin and
define the IL-10-dependent and -independent regulatory properties of skin Bregs during inflammation. Under
Aim 2 we will both determine the trafficking receptor signatures of human skin B cell subsets, including Bregs,
as well as use a model of afferent lymph cannulation in sheep to reveal the relative skin tropism of skin B cell
subsets. The results will allow us to manipulate the localization of anti-inflammatory B cells therapeutically and
to recognize dysregulation of their migration. Finally, under Aim 3, we will block IL-10+ Breg migration into skin
in a model of psoriasiform inflammation, thereby elucidating whether Breg trafficking into skin is essential to
limiting inflammation. We will also evaluate human skin affected by psoriasis for a potential lack of recruited
Bregs. This will determine whether skin recruitment and localization of Bregs are essential for the suppression
of psoriasiform inflammation. In conclusion, this proposal will reveal the migratory routes, employed trafficking
receptors, and anti-inflammatory functions of newly identified cutaneous IL-10+ B cells. Given the wide
association of B cells with a large number of skin pathologies, ranging from inflammation, infection and skin
cancers and the dearth of knowledge about skin B cells, our work will close a significant knowledge gap with
great potential to exploit the gai...

## Key facts

- **NIH application ID:** 9834824
- **Project number:** 5R01AI127389-04
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** Gudrun Philomena Debes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $312,000
- **Award type:** 5
- **Project period:** 2017-01-05 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9834824

## Citation

> US National Institutes of Health, RePORTER application 9834824, Migration and function of cutaneous B cells (5R01AI127389-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9834824. Licensed CC0.

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