Project description:To identify the characters of tissue resident CD4 T cells following influenza virus infection, we sorted lung CD45iv-CD4+CD44hi T cells from influenza PR8 infected mice (28 d.p.i.). Then the cells were performed single cell RNA sequencing. At the result, we found clera 5 differnt clusters and each cluster represent different helper T cell types including TH1, TH17 and Treg. One cluster exhibited both tissue residency and TFH cell features. So, we identify the characters of this hybrid lung CD4 T cells.
Project description:We reported hybrid CD4+ T cell population following influenza viru infection. The hybrid CD4+ T cells exhibit both tissue residency and follicular helper T cell features. To further charaterization, we sorted lung tissue-resident helper T (TRH or TTH) cells (CD45iv-CD4+CD44+GITR-PD1hiFR4hi), non-TRH (CD45iv-CD4+CD44+GITR-PD1lowFR4low), spleen follicalar helper T (TFH) cells (CD4+CD44+GITR-PD1hiCXCR5hi) and non-TFH cells (CD4+CD44+GITR-PD1lowCXCR5low). Then the cells were applied for RNA sequencing. At the resut, we showed tissue-residency related genes are highly enriched in lung TRH but not spleen TFH cells. And The lung TRH cells express higher levels of TFH-related genes than lung-non TRH cells. Therefore, we suggest TRH cells play a role as tissue-resident helper T cells.
Project description:Tissue-resident memory T (TRM) cells are crucial mediators of adaptive immunity in non-lymphoid tissues. However, the functional heterogeneity and pathogenic roles of CD4+ TRM cells that reside within chronic inflammatory lesions remain unknown. We found that CD69hiCD103low CD4+ TRM cells produced effector cytokines and promoted the inflammation and fibrotic responses induced by chronic exposure to Aspergillus fumigatus. Simultaneously, immunosuppressive CD69hiCD103hiFoxp3+ CD4+ regulatory T (Treg) cells were induced and constrained the ability of pathogenic CD103low TRM cells to cause fibrosis. Thus, lung tissue-resident CD4+ T cells play crucial roles in the pathology of chronic lung inflammation, and CD103 expression defines pathogenic effector and immunosuppressive tissue-resident cell subpopulations in the inflamed lung.
Project description:Natural Helper cells constitute a unique lineage of Th2-cytokine producting innate lymphocytes, here we characterize the gene expression profile of non-stimulated or PMA/ionomycin-stimulated Natural Helper cells from naive C57Bl/6 mouse lungs. We used microarrays to detail the gene expression profile of stimulated and unstimulated lung Natural Helper cells in mice. Lineage(-)Sca-1(+)c-Kit(-/low)CD127(+)CD25(+) Lung Natural Helper cells were purified from naive 6-8 week old B6 mice by FACS. RNA was extracted immediately from un-stimulated Natural Helper cells after FACS. Stimulated Natural Helper cells were cultured with PMA/ionomycin for 3 days followed by RNA extraction.
Project description:Allergic asthma develops from allergen exposure in early childhood and progresses into adulthood. The central mediator of progressive allergic asthma is allergen-specific, T helper 2 (Th2) resident memory cells (TRMs). However, whether the immature lung facilitates residence of Th2-TRMs is unknown. Employing a mouse model of progressive allergic inflammation from neonates to adults, we found that maturing sympathetic nerves enable a dopamine-enriched lung environment in early life that promotes establishment of allergen-specific Th2-TRMs. To expore the molecular mechanism, we apply bulk RNA-seq to test the transcriptome changes in mouse Th2 cells after dopamine treatment.
Project description:Chronic graft versus host disease (cGVHD) is a systemic autoimmune-like syndrome. The role of Tph cells in the pathogenesis of cGVHD has not been examined, although previous studies have shown that cGVHD is characterized by loss of Tfh cells. Here, we show that in cGVHD patients and in a murine model that reflects characteristic features of human cGVHD, the proportions of Tph cells among CD4+ T cells in the blood were expanded. These cells augmented memory B cell differentiation and production of IgG via IL-21. Adoptive transfer experiments showed recirculation between Tph in the blood and tissue-resident T helper (Trh) cells in GVHD target tissues. The TCR repertoires of blood Tph cells and Trh cells in GVHD target tissues of mice were highly overlapping.