# IMMUNE MEDIATED ALTERATIONS IN CONNECTIVE TISSUE

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 1991 · $155,181

## Abstract

Scleroderma is characterized by excessive accumulation of collagen and
other matrix components in the skin and visceral organs.  Fibroblasts
isolated from the skin of patients with scleroderma synthesize increased
amounts of collagen, a property that is propagable in vitro.  We previously
demonstrated that normal fibroblast are phenotypically heterogeneous in
their metabolic activity.  The hypothesis that clonal selection of normally
occuring, high collagen synthesizing fibroblasts, is a pathogenetic
mechanism in scleroderma will be used as a working model to examine the
basis for abnormal metabolic activity in this disorder.  Selective
overgrowth of scleroderma fibroblasts may be mediated by products of immune
cells, which infiltrate scleroderma skin, and/or growth factors and other
mediators in the connective tissue environment.  The infiltration of immune
cells, and subsequent mediator release, may be mediated in part by specific
adhesion ligands on lymphocytes and fibroblasts.

We will determine whether scleroderma fibroblasts have abnormal sensitivity
to immune cell derived cytokines and other mediators which regulate bodies
in an attempt to distinguish, based on surface markers, among clonal
fibroblast populations.  In situ studies in scleroderma skin, monoclonal
antibodies which distinguish among clonal fibroblast populations will be
used constituent population, i.e. clonal restriction.  These studies will
be combined with analysis of collagen production by in situ hybridization.
Similar studies will be performed with fibroblast populations cloned from
scleroderma and normal skin.  Finally, to examine a possible basis for
immune cell localization in scleroderma skin, we will examine whether
scleroderma lymphocytes and/or fibroblasts show increased adhesive
properties and whether they express abnormal amounts of the adhesion
ligands LFA-1 and ICAM.

## Key facts

- **NIH application ID:** 3156261
- **Project number:** 5R01AR032343-08
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **SAM.gov UEI:** H6D6JMXJXDE6
- **Principal Investigator:** JOSEPH H KORN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $155,181
- **Award type:** 5
- **Project period:** 1983-04-01 → 1995-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156261

## Citation

> US National Institutes of Health, RePORTER application 3156261, IMMUNE MEDIATED ALTERATIONS IN CONNECTIVE TISSUE (5R01AR032343-08). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3156261. Licensed CC0.

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