Systematic Variations in Immune Response-Related Gene Transcript Abundance Suggest New Questions about Environmental Influences on Lacrimal Gland Immunoregulation

Abstract

Increasing adverse days correlated with increasing abundances of transcripts, including mRNAs for IL-2, IL-10, and CD8, outside the T(H)1/T(H)2 paradigm. The findings raise intriguing questions as to whether and how such changes might be associated with homeostatic phenomena.

Potentially Pathogenic Immune Cells and Networks in Apparently Healthy Lacrimal Glands

“…48 It also had higher abundances of mRNAs for CD4 and CCL21, but not of the other T H 3-reminiscent cluster transcripts; higher abundances of mRNAs for IL-4 and MMP-9 (Figure 10.A); and higher abundances of other transcripts, as well (Figure 10.B, discussed below). Although elevated, the number of RTLA + cells and the abundances of mRNAs for CD4 and CCL21 were in the same proportions as in the other V 61%,27° glands.…”

“…48 For the new analyses described in this report, the medians of the entire samples of values from each group were determined, and the 30-day mean high temperature and the 30-day mean dryness ( $\overline{\mathrm{normal\Delta }\%\mathrm{normalH}}$) were treated as independent variables. The relationships between median abundances and mean daily high temperature and mean daily dryness were tested using the same exponential growth functions listed above, with $\mathrm{normalx}=\overline{false(\mathrm{normal\Delta }\%\mathrm{normalH}false)}$ or x = T̄ $\mathrm{normalx}=\overline{false(\mathrm{normal\Delta }\%\mathrm{normalH}false)}$ or x= T̄.…”

“…48 Of 28 lacrimal glands taken from young adult virgin female rabbits that had been raised in an out-of-doors setting, only one gland presented with obvious immunopathological lesions. However, all glands contained mRNAs that typically are associated with innate inflammatory responses, e.g., CXCL8, IL-1α, IL-1β, and IL-6; mRNAs that function in the ectopic immune inductive tissues characteristic of Sjögren’s- and Mikulicz’s diseases, e.g., CCL21, CXCL13, BAFF, IL-4, and IL-18 49,50 and mRNA for IL-2, which typically is expressed by T H 1 cells.…”

Low humidity environmental challenge causes barrier disruption and cornification of the mouse corneal epithelium via a c-jun N-terminal kinase 2 (JNK2) pathway

“…These findings were accompanied by reduced immunostaining of junctional occludin in the apical corneal epithelium, loss of cell-cell adhesion and increased apical cell desquamation. Mircheff and colleagues have found recently that exposure to adverse environmental conditions can alter cytokine production in the rabbit lacrimal glands (Mircheff, Wang, Thomas et al, 2011). …”

Age-related Defects in Ocular and Nasal Mucosal Immune System and the Immunopathology of Dry Eye Disease

“…For more details on other aspects of DED, such as disruption of homeostatic mechanisms in DED, anti-inflammatory therapy in DED, mucosal autoimmune disease and DED, role of Toll-like receptors in DED, the prevalence and risk factors of DED in the elderly, and relevance of animal models for the research into the immunophysiological processes regulating the functions of the lacrimal gland, we direct the readers to the following excellent reviews by Dana et al, 16,38 Pflugfelder et al, 13 De Paiva et al, 13 McDermott et al, 17,21 Perez et al, 1,39–41 and Mercheff et al 42–44 …”