Multiple Natural and Experimental Inflammatory Rabbit Lacrimal Gland Phenotypes
Austin K Mircheff1, Yanru Wang2, Joel E Schechter3
1Department of Physiology & Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Insights
This study explored lacrimal gland (LG) inflammation diversity. Diverse immune-mediated inflammatory process (IMIP) phenotypes were observed, suggesting phenotype-specific treatments for LG disorders.
Area of Science:
- Ophthalmology and immunology research.
- Investigating autoimmune disease mechanisms in ocular adnexa.
Background:
- Lacrimal gland (LG) dysfunction can lead to dry eye disease.
- Understanding the immunophysiology of the LG is crucial for diagnosing and treating inflammatory conditions.
Purpose of the Study:
- To investigate the diversity of immunophysiological and immune-mediated inflammatory process (IMIP) phenotypes in the lacrimal gland.
- To explore the relationship between pre-adoptive transfer immune markers and post-adoptive transfer IMIP features.
Main Methods:
- Dendritic cells loaded with acinar cell microparticles were used to induce autoimmune responses in rabbit lacrimal glands.
- Immune cell activation, autoantibody titers, and clinical eye tests (Schirmer, Rose Bengal) were assessed.
- Histopathology, immunohistochemistry, and transcript abundance analysis were performed, followed by Principal Component Analysis (PCA).
Main Results:
- Adoptive transfer of activated lymphocytes induced IMIP in lacrimal glands, with varying severity.
- Previous immunization exacerbated the autoimmune response and lacrimal gland atrophy.
- PCA revealed diverse immunophysiological and IMIP phenotypes, with significant associations between pre-transfer immune status and post-transfer IMIP features.
Conclusions:
- The inherent variability in normal lacrimal gland states may contribute to the observed diversity in experimental IMIP phenotypes.
- Characterizing these diverse phenotypes could pave the way for developing targeted diagnostic and therapeutic strategies for lacrimal gland disorders.
Purpose:
To investigate lacrimal gland (LG) immunophysiological and immune-mediated inflammatory process (IMIP) phenotype diversity.
Methods:
Ex vivo matured dendritic cells (mDC) were loaded with acinar cell microparticles (MP). Peripheral blood lymphocytes (PBL) were activated in mixed cell reactions with mDC and injected directly into autologous, unilateral LG (1°ATD-LG) of two rabbit cohorts, one naïve, one immunized with a LG lysate membrane fraction (Pi). Autoimmune IgG titers were assayed by ELISA, MCR PBL stimulation indices (SI) by [3H]-thymidine incorporation. Schirmer tests without and with topical anesthetic (STT-I, STT-IA) and rose Bengal (RB) staining tests were performed. H&E and immunohistochemically stained sections were examined. RNA yields and selected transcript abundances were measured. Immune cell number and transcript abundance data were submitted to Principal Component Analysis (PCA).
Results:
Immunizing Pi dose influenced SI but not IgG titers. STT scores were decreased, and rose Bengal scores increased, by day 118 after immunization. Previous immunization exacerbated scores in 1°ATD-eyes and exacerbated 1°ATD-LG atrophy. IMIP were evident in 2°ATD-LG as well as 1°ATD-LG. PCA described diverse immunophysiological phenotypes in control LG and diverse IMIP phenotypes in ATD-LG. IgG titers and SI pre-adoptive transfer were significantly associated with certain post-adoptive transfer IMIP phenotype features, and certain LG IMIP features were significantly associated with RB and STT IA scores.
Conclusions:
The underlying variability of normal states may contribute to the diversity of experimental IMIP phenotypes. The ability to generate and characterize diverse phenotypes may lead to phenotype-specific diagnostic and therapeutic paradigms.
