Biology subjects

de Ocampo, C.

Publications and source records attributed to de Ocampo, C..

3 recordsLinked to original sources

bioRxiv2025

Effect of Age on Xenobiotic-Induced Autoimmunity

Aging is associated with increased spontaneous autoantibody production and chronic inflammation, yet its impact on xenobiotic-induced autoimmunity remains unexplored. This study investigates the effect of age on mercury-induced autoimmunity (HgIA) in B10.S mice, a model of xenobiotic-induced autoimmunity characterized by anti-nucleolar autoantibodies (ANoA). Mature (3 months), adult (6 months), middle-aged (12 months), and old-age (24 months) mice were exposed to mercury (HgCl2) or phosphate-buffered saline (PBS) for 4-5 weeks. While spontaneous anti-nuclear antibodies (ANA) increased with age in PBS-treated mice (34% in middle-aged, 57% in old age mice), HgIA incidence declined in old age mice, with only 59% (26/44) developing significant ANoA titers compared to 91-100% in younger cohorts. Notably, 56% (10/18) of initially ANoA-negative old mice had detectable ANoA at a lower dilution, indicating a reduced but not absent response. ANoA negativity in old age mice was associated with lower immunoglobulin levels, reduced anti-chromatin antibodies, and diminished germinal center formation, suggestive of immunosenescence. Flow cytometry revealed age-related declines in CD4 T cells, with mercury exposure augmenting T-cell differentiation in younger but not old mice. These findings demonstrate that aging enhances spontaneous autoimmunity but impairs xenobiotic-induced autoimmunity, with a subset of old age mice retaining partial responsiveness at lower dilutions, highlighting the complex interplay between immunosenescence and environmental triggers.

immunology↗

bioRxiv2025

Crystalline silica exposure induces multiple systemic autoimmune phenotypes including inflammatory arthritis and nephritis in Collaborative Cross mice with differing sub-clinical autoimmune profiles.

Inhalation of crystalline silica dust, an occupational hazard, has been strongly associated with the development of autoimmune connective tissue diseases, such as rheumatoid arthritis and systemic lupus erythematosus. However, it remains unclear if silica-mediated autoimmune disease requires preexisting subclinical autoimmunity, and to what extent the severity of the preexisting condition influences silica-induced disease. The aim of the current study was to examine whether silica-mediated autoimmune disease requires preexisting subclinical autoimmunity, using the Collaborative Cross (CC) mouse model system, recognized for its ability to mimic the genetic diversity observed in human populations. Sixty-one CC strains were assessed for the presence of subclinical autoimmunity via autoantibodies and inflammatory markers. Six CC strains, chosen to represent a range of subclinical autoimmunity, were exposed transorally to 5 mg silica or PBS and examined 12 weeks later for lung inflammation, autoantibody responses, total immunoglobulin levels, and the manifestation of glomerulonephritis and autoimmune arthritis. Results indicated a spectrum of spontaneous subclinical autoimmunity among naive CC strains, with silica exposure leading to significant pulmonary inflammation and systemic autoimmunity, including glomerulonephritis and synovitis. Notably, strains with pre-existing subclinical autoimmunity showed more severe disease outcomes post-exposure.

immunology↗

bioRxiv2025

Silica-mediated exacerbation of inflammatory arthritis: A novel murine model

ObjectiveThe mucosal origin hypothesis in rheumatoid arthritis (RA) posits that inhalant exposures, such as cigarette smoke and crystalline silica (c-silica), trigger immune responses contributing to disease onset. Despite the established risk posed by these exposures, the mechanistic link between inhalants, lung inflammation, and inflammatory arthritis remains poorly understood, partly from the lack of a suitable experimental model. As c-silica accelerates autoimmune phenotypes in lupus models and is a recognized risk factor for several autoimmune diseases, we investigated whether c-silica exposure could induce RA-like inflammatory arthritis in mice. MethodsTwo arthritis-prone mouse strains, BXD2/TyJ and HLA-DR4 transgenic (DR4-Tg), were exposed to c-silica or PBS via oropharyngeal instillation. Arthritis was evaluated by clinical signs and histopathology. Autoimmunity was further evaluated by serological analysis, including autoantibodies and cytokines and chemokines. Lung pathology was evaluated by histopathology and immunofluorescent staining for lymphocyte and macrophages. ResultsC-silica exposure induced chronic pulmonary silicosis in all mice. In BXD2 mice, this was associated with rapid arthritis development, marked by synovitis, bone erosion, and elevated serum autoantibody levels targeting various antigens, including snRNP and citrullinated protein. Additionally, BXD2 mice exhibited inducible bronchus-associated lymphoid tissue (iBALT) formation and elevated autoantibodies in bronchoalveolar lavage fluid (BALF). Conversely, DR4-Tg mice had no significant arthritis, negligible autoantibody responses, and milder lung inflammation lacking iBALT. ConclusionWe introduce a novel model of c-silica-mediated inflammatory arthritis, creating a novel platform to unravel the molecular and cellular underpinnings of RA and advance understanding of the mucosal origin hypothesis. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=133 SRC="FIGDIR/small/631488v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@88080aorg.highwire.dtl.DTLVardef@c7d935org.highwire.dtl.DTLVardef@8548d3org.highwire.dtl.DTLVardef@703ceb_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗