# IMMUNOREGULATION IN AVIAN SCLERODERMA

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 1993 · $133,125

## Abstract

University of California (UCD) line 200 (L200) chickens develop an
inherited auto-immune fibrotic disease associated with autoantibodies and
features similar to human progressive systemic sclerosis.  Early in life
L200 chickens develop T cell infiltrates in the skin, followed by severe
dermal fibrosis and vascular occlusions.  In birds that survive this
initial episode of disease, a chronic course follows with the development
of fibrosis, mononuclear cell infiltration and vascular alterations in
the esophagus, small intestine, lungs, kidneys, heart, and testes.  We
have, during the current period of the grant, demonstrated that L200
chickens have a major developmental defect in type I thymic epithelium
recognized by our monoclonal antibody MUI 70.  The antigen recognized by
MUI 70 is absent in L200 type I thymic epithelium but is found in all
other normal chicken strains examined.  Furthermore, MUI 70 is also
expressed in the epidermis of normal chickens but is absent in L200
animals.  We now propose to investigate in detail the relationship
between the presence (or absence) of MUI 70+ stromal element and T cell
differentiation, by its expression during T cell development in ovo in
embryonic thymic organ cultures, and by doing embryonic thymic
transplants.  We also postulate that MUI 70, a conserved antigen,
recognizes a cytoskeletal component of a distinct subset of epithelial
cells.  Its generalized function may be in restricted cell-cell
interactions or adhesions and in the thymus, in particular, it may
mediate one of the earliest interactions between incoming precursors
(located near type I epithelium) and thymic stroma.  To explain the
dermal pathology observed in L200 birds, we have demonstrated that
fibroblast cultures derived from fibrotic skin of diseased L200 chickens
display an activated phenotype producing elevated quantities of collagen,
non-collagenous protein, and glycosaminoglycans (GAG).  Moreover,
supernatants constitutively generated by culturing mononuclear cells
isolated from fibrotic skin lesions of L200 chickens contain a 24 kD
cytokine that stimulates fibroblast collagen synthesis and a 28 kD
cytokine that stimulates fibroblast GAG synthesis.  We will characterize
these cytokines and concurrently study the alterations in L200 cultured
vascular smooth muscle cells and vascular endothelial cells.  Hence, we
propose that L200 chickens have a developmental defect in type I thymic
epithelium which induces abnormal thymocyte differentiation and
maturation, thereby predisposing them to autoimmune disease with
resultant fibrotic and vascular pathology in the dermis and other organs.

## Key facts

- **NIH application ID:** 3157789
- **Project number:** 2R01AR036867-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **SAM.gov UEI:** TX2DAGQPENZ5
- **Principal Investigator:** MERRILL E GERSHWIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $133,125
- **Award type:** 2
- **Project period:** 1987-07-01 → 1997-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3157789

## Citation

> US National Institutes of Health, RePORTER application 3157789, IMMUNOREGULATION IN AVIAN SCLERODERMA (2R01AR036867-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3157789. Licensed CC0.

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