Biology subjects

Chauhan, S. K.

Publications and source records attributed to Chauhan, S. K..

4 recordsLinked to original sources

bioRxiv2026

Preferential Isoform Usage and Isoform Switching in Systemic Lupus Erythematosus Patients with Distinct Autoantibody Profile

RNA sequencing has advanced our understanding of molecular heterogeneity in systemic lupus erythematosus (SLE), yet most studies have focused on differential gene expression (DGE), which overlooks transcript-level complexity. Alternative splicing and polyadenylation generate multiple isoforms from a single gene, and their dysregulation may contribute to autoimmune pathogenesis, including through the production of non-canonical isoforms with potential autoantigenic properties. To explore this underexamined dimension, we analysed differential isoform usage (DIU) and major isoform switching (MIS) across SLE subgroups stratified by autoantibody profile: anti-dsDNA+, anti-ENA+ and anti-dsDNA+ENA+. Subgroup-specific DIU and MIS events were enriched in RNA-binding and transcription-related functions. In the anti-dsDNA+ subgroup, the T-cell receptor adaptor GRAP2 showed isoform switching accompanied by expansion of a non-coding retained-intron transcript. In the anti-ENA+ subgroup, IGHM switched from the membrane-bound to the secretory form, consistent with an antibody-secreting cell signature; NACA, a reported IgE autoantigen, showed isoform switching; and BRI3, linked to TNF--induced cell death, switched toward its protein-coding transcript. In the anti-dsDNA+ENA+ subgroup, TNFAIP2, a TNF--induced gene, showed isoform redistribution with loss of a uORF-containing transcript. These findings highlight isoform regulation as a distinct, subgroup-specific and functionally relevant layer of transcriptomic dysregulation in SLE.

immunology↗

bioRxiv2025

CD38hiCD19dim cells in lymph nodes predict favorable prognosis in patients with stage III melanoma receiving adjuvant PD-1-blockade

BackgroundAdjuvant immunotherapy has significantly improved survival for patients with stage III cutaneous melanoma, yet a fraction of patients will not benefit from immune checkpoint inhibitors (ICI). The tumor microenvironment plays a pivotal role in generating durable responses to ICI. By analyzing the cellular composition of tumor-associated subsets, key immune components essential for promoting an anti-tumor environment can be pinpointed. This will allow for both patient stratification and identification of biomarkers associated with improved patient outcome. MethodRegional lymph nodes were obtained from patients with stage III melanoma at surgery (n=29). Patients eligible for anti-PD-1 therapy (PD-1; pembrolizumab or nivolumab) received adjuvant treatment for up to one year. CyTOF was used to determine cellular composition in pre-treatment surgical specimens. Bulk gene expression data generated by NanoString from patients receiving surgery without adjuvant therapy (n=125) was implemented for evaluating trends observed in the CyTOF dataset. ResultsAlthough no significant differences were observed across major hierarchical immune cell types between patients who developed distant metastasis after surgery and those that did not, an increased proportion of CD103+PD-1+CD8+ (TRM) T cells and plasmablast-like CD38hiCD19dim cells were associated with improved prognosis in the CyTOF cohort. In the untreated cohort, a subset of patients defined as "Ultra-cold" (< 2.5 % tumor-infiltrating lymphocyte (TIL) scored by a pathologist) had significantly worse outcome than those with higher TIL infiltration. This Ultra-cold TIL group was associated with reduced B cell score, but not CD8+ T cell score, as well as reduced expression of activation genes like CD38. ConclusionIn this study, CD103+PD-1+CD8+ (TRM) T cells and plasmablast-like CD38hiCD19dim cell populations were found to be strongly associated with prolonged distant metastasis-free survival in regional lymph nodes from patients with stage III melanoma treated with PD-1. This suggests an association between progression and infiltration of these cell types at baseline and highlights the potential of using immune cell subsets as prognostic biomarkers. What is already known on this topic - Patients being diagnosed with stage III melanoma will receive immune checkpoint inhibitors but will often be cured by surgery alone. Selection of which patients might benefit from treatment is still unresolved. Accurate biomarkers would aid in treatment stratification, to avoid overtreatment, and unnecessary toxicities. What this study adds - This study highlights how baseline CD103+PD-1+CD8+ (TRM) T cells and plasmablast-like CD38hiCD19dim cell populations in the regional lymph node, is strongly associated with improved outcome in patients receiving anti-PD-1 therapy. How this study might affect research, practice or policy - The strong association between baseline plasmablast-like cell infiltration in RLN and prolonged distant metastasis free- survival, highlights this cell type as a potential treatment stratification criterion to identify patients with good prognosis.

cancer biology↗

bioRxiv2020

The human small intestine comprises two subsets of regulatory Foxp3+ CD4 T cells with very different life span and functional properties.

BackgroundRegulatory CD4 T cells (Tregs) in the mice gut are mainly specific for intestinal antigens and play an important role in the suppression of immune responses against harmless dietary antigens and members of the microbiota. However, information about the phenotype and function of Tregs in the human gut is limited. ObjectiveHere, we performed a detailed characterization of Foxp3+ CD4 Tregs in the human small intestine. MethodsTregs and conventional CD4 T cells derived from normal intestine as well as from transplanted duodenum and celiac disease lesions were subjected to extensive immunophenotyping and their suppressive activity and ability to produce cytokines were assessed. ResultsSmall intestinal Foxp3+ CD4 T cells were CD45RA- CD127- CTLA4+ and suppressed proliferation of autologous T cells. Approximately 60% of the Tregs expressed the transcription factor Helios. When stimulated, Helios- Tregs produced IL-17, IFN-{gamma} and IL-10, whereas Helios+ Tregs produced very low levels of these cytokines. By sampling mucosal tissue from transplanted human duodenum we demonstrated that donor Helios+ Tregs have a short life span whereas Helios- Tregs persisted for at least 1 year post-transplantation. In normal small intestine, Foxp3+ Tregs constituted only 2% of all CD4 T cells, while in active celiac disease both subsets expanded 5-10-fold. ConclusionThe small intestine contains two subsets of Tregs with different functional capacities and very different life span. Both subsets are scarce in the normal situation but increase dramatically in a chronic inflammatory setting.

immunology↗

bioRxiv2019

Resident memory CD8 T cells persist for years in human small intestine

In human small intestine, most CD8 T cells in the lamina propria and epithelium express a resident memory (Trm) phenotype and persist for at least one year in transplanted tissue. Intestinal CD8 Trm cells have a clonally expanded immune repertoire that is stable over time and exhibit enhanced protective capabilities. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/553792v1_ufig1.gif" ALT="Figure 1"> View larger version (98K): org.highwire.dtl.DTLVardef@10c19aaorg.highwire.dtl.DTLVardef@168e86forg.highwire.dtl.DTLVardef@73f0f5org.highwire.dtl.DTLVardef@1d08d10_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIThe vast majority of CD8 T cells in the human small intestine are Trm cells C_LIO_LICD8 Trm cells persist for >1 year in transplanted duodenum C_LIO_LIIntraepithelial and lamina propria CD8 Trm cells show highly similar TCR repertoire C_LIO_LIIntestinal CD8 Trm cells efficiently produce cytokines and cytotoxic mediators C_LI

immunology↗