Deficiency of DOCK2 delays development of spontaneous uveoretinitis in a lymphopenic mouse model of colitis
- 1School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen
- 2Department of Ophthalmology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences
- 3Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University
Abstract
Spontaneous experimental autoimmune uveoretinitis (EAU) in double-transgenic (dTg) mice expressing retinal Hen Egg Lysozyme (HEL) and HEL-specific T cell receptor CD4 T cells is a severe CD4⁺ T cell-driven disease, occurs in 100% of dTg mice at post-partum day (p)20/21 and is accompanied by post-EAU colitis. Because DOCK2 (Dedicator of cytokinesis 2) is essential for Rac-dependent immune cell function, including T cell motility and migration from secondary lymphoid tissues, we investigated its effect on T cell behaviour in this model. dTg mice lacking DOCK2 (DOCK2⁻/⁻ dTg) were examined for evidence of uveitis (fundoscopy, histology and flow cytometry) and intestinal inflammation (colon length and histology). Retinal inflammation and ocular CD4⁺ T cell infiltration were assessed over time. Flow cytometry of lamina propria cells quantified CD4⁺ T cells and determined the balance of Helios+ versus Helios− regulatory T cells. The eye-draining lymph nodes were also analysed for CD4⁺ T cell populations. DOCK2⁻/⁻ dTg mice showed delayed and attenuated uveitis. Retinal inflammation, consistently evident by p21 in DOCK2+/+ dTg mice, and atrophy (~ p30) were absent until ~p60 and were associated with markedly reduced ocular CD4⁺ T cell infiltration. Despite profound lymphopenia, DOCK2 deficiency did not induce spontaneous colitis; colons were normal in length and lacked inflammation. Flow cytometry of lamina propria cells showed no change in overall CD4⁺ T cell numbers between DOCK2⁻/⁻ and DOCK2⁺/⁺ mice. However, the balance of Helios expression in Treg was altered, with DOCK2⁻/⁻ mice containing significantly higher numbers of Helios− Treg in the lamina propria compared to DOCK2+/+ mice. In contrast, peripheral lymphoid tissues (eye-draining lymph nodes), showed disproportionately reduced CD4⁺ T cell numbers in DOCK2⁻/⁻ dTg mice. We conclude DOCK2 may be a potential target for control of uveoretinitis via expansion of eye-homing gut Helios− Treg.
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BibTeX
@article{molzer2026deficiency,
title = {{Deficiency of DOCK2 delays development of spontaneous uveoretinitis in a lymphopenic mouse model of colitis}},
author = {Christine Mölzer and Izabela P. Klaska and Tian Yu and Rosie Fordyce and Elizabeth Muckersie and Yoshinori Fukui and John V. Forrester and Lucia Kuffova},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-62501-7},
url = {https://doi.org/10.1038/s41598-026-62501-7},
note = {CC BY},
}
RIS
TY - JOUR
TI - Deficiency of DOCK2 delays development of spontaneous uveoretinitis in a lymphopenic mouse model of colitis
AU - Christine Mölzer
AU - Izabela P. Klaska
AU - Tian Yu
AU - Rosie Fordyce
AU - Elizabeth Muckersie
AU - Yoshinori Fukui
AU - John V. Forrester
AU - Lucia Kuffova
PY - 2026
DA - 2026/07/01
JO - Scientific Reports
DO - 10.1038/s41598-026-62501-7
UR - https://doi.org/10.1038/s41598-026-62501-7
AB - Spontaneous experimental autoimmune uveoretinitis (EAU) in double-transgenic (dTg) mice expressing retinal Hen Egg Lysozyme (HEL) and HEL-specific T cell receptor CD4 T cells is a severe CD4⁺ T cell-driven disease, occurs in 100% of dTg mice at post-partum day (p)20/21 and is accompanied by post-EAU colitis. Because DOCK2 (Dedicator of cytokinesis 2) is essential for Rac-dependent immune cell function, including T cell motility and migration from secondary lymphoid tissues, we investigated its effect on T cell behaviour in this model. dTg mice lacking DOCK2 (DOCK2⁻/⁻ dTg) were examined for evidence of uveitis (fundoscopy, histology and flow cytometry) and intestinal inflammation (colon length and histology). Retinal inflammation and ocular CD4⁺ T cell infiltration were assessed over time. Flow cytometry of lamina propria cells quantified CD4⁺ T cells and determined the balance of Helios+ versus Helios− regulatory T cells. The eye-draining lymph nodes were also analysed for CD4⁺ T cell populations. DOCK2⁻/⁻ dTg mice showed delayed and attenuated uveitis. Retinal inflammation, consistently evident by p21 in DOCK2+/+ dTg mice, and atrophy (~ p30) were absent until ~p60 and were associated with markedly reduced ocular CD4⁺ T cell infiltration. Despite profound lymphopenia, DOCK2 deficiency did not induce spontaneous colitis; colons were normal in length and lacked inflammation. Flow cytometry of lamina propria cells showed no change in overall CD4⁺ T cell numbers between DOCK2⁻/⁻ and DOCK2⁺/⁺ mice. However, the balance of Helios expression in Treg was altered, with DOCK2⁻/⁻ mice containing significantly higher numbers of Helios− Treg in the lamina propria compared to DOCK2+/+ mice. In contrast, peripheral lymphoid tissues (eye-draining lymph nodes), showed disproportionately reduced CD4⁺ T cell numbers in DOCK2⁻/⁻ dTg mice. We conclude DOCK2 may be a potential target for control of uveoretinitis via expansion of eye-homing gut Helios− Treg.
SN - 2045-2322
ER -