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T/B-cell interactions are more transient in response to weak stimuli in SLE-prone mice.

ABSTRACT: Changes in immune function during the course of systemic lupus erythematosus (SLE) are well characterized. Class-switched antinuclear antibodies are the hallmark of SLE, and T/B-cell interactions are thus critical. However, changes in immune function contributing to disease susceptibility are unknown. Here, we have analyzed primary T and B cells from a mouse model of SLE prior to the onset of disease. To allow cognate T-cell activation with low affinity, we have developed a lower potency peptide ligand for the OTII TCR. T- and B-cell couples formed less frequently and retained their polarity less efficiently preferentially in response to low-affinity stimulation in SLE-prone mice. This matched decreased recruitment of actin and Vav1 and an enhanced PKC? recruitment to the cellular interface in T cells. The induction of the GC B-cell marker GL7 was increased in T/B cell couples from SLE-prone mice when the T-cell numbers were limited. However, the overall gene expression changes were marginal. Taken together, the enhanced cell-couple transience may allow a more efficient sampling of a large number of T/B cell couples, preferentially in response to limiting stimuli, therefore enhancing the immune reactivity in the development of SLE.

SUBMITTER: Sinai P

PROVIDER: S-EPMC4261040 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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T/B-cell interactions are more transient in response to weak stimuli in SLE-prone mice.

Sinai Parisa P Dozmorov Igor M IM Song Ran R Schwartzberg Pamela L PL Wakeland Edward K EK Wülfing Christoph C

European journal of immunology 20141112 12

Changes in immune function during the course of systemic lupus erythematosus (SLE) are well characterized. Class-switched antinuclear antibodies are the hallmark of SLE, and T/B-cell interactions are thus critical. However, changes in immune function contributing to disease susceptibility are unknown. Here, we have analyzed primary T and B cells from a mouse model of SLE prior to the onset of disease. To allow cognate T-cell activation with low affinity, we have developed a lower potency peptide ...[more]

PMID: 25209945

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Project description:The gut mycobiota (fungal microbiota) plays a crucial role in the immune system, potentially impacting autoimmune diseases such as systemic lupus erythematosus (SLE). Despite growing interest, data on intestinal fungi in SLE remain limited. This study thereby investigated the human-mimicked (mice) gut mycobiome and quantitative gut mycobiome analyses using universal fungal internal transcribed spacer 2 (ITS2) DNA next generation sequencing and real-time PCR, tracking time-series dynamics from preclinical to established SLE conditions in two SLE-prone mouse models. These models included pristane -induced mice, representing an environmental cause of SLE, and Fc gamma receptor RIIb (FcgRIIb) deficiency mice, representing a genetic factor. Fecal samples and different intestinal sections from mice aged 2-10 months were analyzed, including samples from 4-month-old and 11-month-old mice, which represented preclinical lupus (negative for anti-dsDNA) and established SLE conditions (positive for anti-dsDNA with proteinuria), respectively, alongside age-matched healthy controls. Results showed increased fungal diversity, specific changes in gut fungal species (i.e. increased Candida spp.), and an elevated Basidiomycota-to-Ascomycota (Basidiomycota/Ascomycota) ratio, which correlated with lupus activity in both lupus models. Linear discriminant analysis Effect Size (LEfSe; a possible representative organism) helped identify specific fungal difference between the lupus models. Our findings revealed that active lupus states may elevate gut fungal populations and alter fungal components in both the pristane and genetically susceptible SLE-prone mice, as indicated by mycobiota and quantitative mycobiota analyses. These changes could, in turn, influence disease activity. This research is essential for a deeper understand of the SLE-gut microbiome association, as the gut microbiome comprises both bacterial and fungal symbiosis. Manipulating fungal communities could present a potential therapeutic avenue for influencing disease outcomes in lupus. Further studies are crucial to clarify the direct role of gut fungi in lupus disease progression.

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T/B-cell interactions are more transient in response to weak stimuli in SLE-prone mice.

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T/B-cell interactions are more transient in response to weak stimuli in SLE-prone mice.

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