The Tetraspanin Protein CD37 Regulates IgA Responses and Anti-Fungal Immunity

Immunoglobulin A (IgA) secretion by plasma cells in the immune system is critical for protecting the host from environmental and microbial infections. However, the molecular mechanisms underlying the generation of IgA+ plasma cells remain poorly understood. Here, we report that the B cell–expressed tetraspanin CD37 inhibits IgA immune responses in vivo. CD37-deficient (CD37−/−) mice exhibit a 15-fold increased level of IgA in serum and significantly elevated numbers of IgA+ plasma cells in spleen, mucosal-associated lymphoid tissue, as well as bone marrow. Analyses of bone marrow chimeric mice revealed that CD37–deficiency on B cells was directly responsible for the increased IgA production. We identified high local interleukin-6 (IL-6) production in germinal centers of CD37−/− mice after immunization. Notably, neutralizing IL-6 in vivo reversed the increased IgA response in CD37−/− mice. To demonstrate the importance of CD37—which can associate with the pattern-recognition receptor dectin-1—in immunity to infection, CD37−/− mice were exposed to Candida albicans. We report that CD37−/− mice are evidently better protected from infection than wild-type (WT) mice, which was accompanied by increased IL-6 levels and C. albicans–specific IgA antibodies. Importantly, adoptive transfer of CD37−/− serum mediated protection in WT mice and the underlying mechanism involved direct neutralization of fungal cells by IgA. Taken together, tetraspanin protein CD37 inhibits IgA responses and regulates the anti-fungal immune response

Jeito de mulher rural: a busca de direitos sociais e da igualdade de gênero no Rio Grande do Sul

Este trabalho trata de processos emancipatórios de mulheres, em especial de pequenas agricultoras no sul do Brasil, no Movimento de Mulheres Trabalhadoras Rurais do Rio Grande do Sul - MMTR-RS. A vida diária das agricultoras nos providencia elementos cruciais para entender a sua ação social, sendo o âmbito em que se produzem os significados culturais. Além disso, o enfoque na vida diária revela o impacto dos contextos históricos, econômicos, religiosos e políticos específicos em que a ação social acontece e nos ajuda a entender como as participantes chegam a problematizar demandas coletivas e a desafiar a arena política

Jeito de mulher rural: a busca de direitos sociais e da igualdade de gênero no Rio Grande do Sul

Este trabalho trata de processos emancipatórios de mulheres, em especial de pequenas agricultoras no sul do Brasil, no Movimento de Mulheres Trabalhadoras Rurais do Rio Grande do Sul – MMTR-RS. A vida diária das agricultoras nos providencia elementos cruciais para entender a sua ação social, sendo o âmbito em que se produzem os significados culturais. Além disso, o enfoque na vida diária revela o impacto dos contextos históricos, econômicos, religiosos e políticos específicos em que a ação social acontece e nos ajuda a entender como as participantes chegam a problematizar demandas coletivas e a desafiar a arena política

Protein expression of tetraspanins on murine DC subsets.

<p>(A) Flow cytometric analysis of total tetraspanin protein expression on DC subsets. Cells from spleen were enriched for DCs as described in the materials and methods. Far left: dot plots of viable CD11c+ cells (CD4+ and CD8α+ DCs) or viable pDCs. CD4+ DCs were identified as CD4+CD11b+, CD8α+ DCs as CD8α+CD11b-, and pDCs as B220+CD11c^int cells. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184317#pone.0184317.s006" target="_blank">S3 Fig</a> for full gating strategy. Histograms of tetraspanin protein expression on gated cells depicted in the dot plots (black line) and isotype controls (grey line). (B) Average tetraspanin expression of 3 individual mice, geometric mean fluorescence intensity (gMFI) normalized for isotype control binding, each symbol represents one mouse. P-values displayed above each plot represent the result of ANOVA to which multiple testing correction was been applied (n.s. = non-significant). * p<0.05, ** p< 0.01 ***p<0.001 by post-hoc t-testing. See also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184317#pone.0184317.s002" target="_blank">S2 Table</a> for full results of the statistical analysis.</p

Relative mRNA expression levels of tetraspanins in murine DC subsets.

<p>Z-scored values of (A) differentially expressed genes (ANOVA p<0.05) and (B) non-differentially expressed genes (ANOVA p>0.05 and expression > 2⁵ in at least two mice in one subset). Asterisks mark genes that were selected for further analysis. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184317#pone.0184317.s001" target="_blank">S1 Table</a> for selected probes and statistics on expression data of all members of the tetraspanin family. (C) Gene expression levels of tetraspanins in DC subsets, probe intensities are plotted, each symbol represents one mouse. P-values displayed above each plot represent the result of ANOVA to which multiple testing correction was been applied (n.s. = non-significant). * p<0.05, ** p< 0.01 ***p<0.001 by post-hoc t-testing. See also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184317#pone.0184317.s001" target="_blank">S1 Table</a> for full results of the statistical analysis.</p

Tetraspanin protein expression on DC subsets.

<p>Tetraspanin protein expression on DC subsets.</p

Protein expression of tetraspanins on human DC subsets.

<p>(A) Flow cytometric analysis of total tetraspanin protein expression on fixed permeabilized DC subsets. Far left: dot plots of viable Lin-MHC II+ cells. CD1c+ DCs were identified as BDCA1+, CD141+ DCs as BDCA3+, and pDCs as BDCA4+ cells. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184317#pone.0184317.s005" target="_blank">S2 Fig</a> for full gating strategy. Histograms of tetraspanin expression (black curve) and isotype control staining (grey curve) on gated cells depicted in the dot plots. (B) Tetraspanin expression of 3 healthy donors, geometric mean fluorescence intensity (gMFI) normalized for isotype control binding, each symbol represents one donor. P-values displayed above each plot represent the result of ANOVA to which multiple testing correction was been applied (n.s. = non-significant). * p<0.05, ** p< 0.01 ***p<0.001 by post-hoc t-testing. See also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184317#pone.0184317.s002" target="_blank">S2 Table</a> for full results of the statistical analysis.</p