Distinct use of super-enhancer elements controls cell type-specific CD25 transcription and function.

The IL-2 receptor α chain (IL-2Rα/CD25) is constitutively expressed on double-negative (DN2/DN3 thymocytes and regulatory T cells (T) but induced by IL-2 on T and natural killer (NK) cells, with expression regulated by a STAT5-dependent super-enhancer. We investigated CD25 regulation and function using a series of mice with deletions spanning STAT5-binding elements. Deleting the upstream super-enhancer region mainly affected constitutive CD25 expression on DN2/DN3 thymocytes and T, with these mice developing autoimmune alopecia, whereas deleting an intronic region decreased IL-2-induced CD25 on peripheral T and NK cells.

Macrophage-mediated extracellular matrix remodeling controls host Staphylococcus aureus susceptibility in the skin.

Hypodermis is the predominant site of Staphylococcus aureus infections that cause cellulitis. Given the importance of macrophages in tissue remodeling, we examined the hypodermal macrophages (HDMs) and their impact on host susceptibility to infection. Bulk and single-cell transcriptomics uncovered HDM subsets with CCR2-dichotomy.

TCF3 haploinsufficiency defined by immune, clinical, gene-dosage, and murine studies.

Background: TCF3 is a transcription factor contributing to early lymphocyte differentiation. Germline monoallelic dominant negative and biallelic loss-of-function (LOF) null TCF3 mutations cause a fully penetrant severe immunodeficiency. We identified 8 individuals from 7 unrelated families with monoallelic LOF TCF3 variants presenting with immunodeficiency with incomplete clinical penetrance.

Flow cytometry analysis of the subpopulations of mouse keratinocytes and skin immune cells.

Skin is our body's outermost physical barrier and an immunological interface enriched with various immune and non-immune cells. However, efficient generation of single-cell suspensions for flow cytometry analysis can be challenging. Here, we provide protocols to obtain epidermal and whole skin cell suspensions as well as gating strategies to identify mouse keratinocytes and skin immune cell subsets via flow cytometry.

CARD9 Expression Pattern, Gene Dosage, and Immunodeficiency Phenotype Revisited.

Background: CARD9 deficiency is an autosomal recessive primary immunodeficiency underlying increased susceptibility to fungal infection primarily presenting as invasive CNS Candida and/or cutaneous/invasive dermatophyte infections. More recently, a rare heterozygous dominant negative CARD9 variant c.1434 + 1G > C was reported to be protective from inflammatory bowel disease.

Single-nucleotide polymorphism and haplotype analysis of macrophage migration inhibitory factor gene and its correlation with serum macrophage migration inhibitory factor levels in North Indian psoriatic patients with moderate disease severity: A cross-sectional study.

Background: Psoriasis is associated with significant morbidity and impaired quality of life. Identification of the host genes that influence disease susceptibility and can potentially guide future, targeted therapy is the need of the hour.

Aims: The aim of the study was to investigate the associations of macrophage migration inhibitory factor (MIF) gene polymorphisms, that is, a 5-8-CATT tetra nucleotide repeats at -794 (-794*CATT5-8) and a single-nucleotide polymorphism at -173 (-173*G/C) with the risk of chronic plaque psoriasis and to observe the correlation, if any, of disease determinants with genetic functional variants and circulating MIF levels.

Correction to: A Nonsense N -Terminus NFKB2 Mutation Leading to Haploinsufficiency in a Patient with a Predominantly Antibody Deficiency.

Due to typesetting mistake, the caption of Figure 2 was mistakenly replaced with the caption of Figure 3.

Expression of CD40 Ligand on T Cells and Soluble CD40 Ligand in Children With Kawasaki Disease: A Single-Center Preliminary Study From North India.

Background/objective: This study was done to examine the role of CD40 ligand (CD40L) in children with Kawasaki disease (KD). There is paucity of literature on this aspect of KD.

Methods: This was a case-control study of patients with KD diagnosed at the Allergy Immunology Unit, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Clinical and molecular features of X-linked hyper IgM syndrome - An experience from North India.

X-linked hyper IgM Syndrome (XLHIGM), the most frequent form of the Hyper IgM syndromes is a primary immune deficiency resulting from a mutation in the CD40 ligand gene (CD40LG). We analyzed the clinical and laboratory features of ten patients with XLHIGM, who were diagnosed at a tertiary care hospital in North India. Most common infections were sinopulmonary infections (80%) and diarrhea (50%).

STAT3-Mediated Transcriptional Regulation of Osteopontin in STAT3 Loss-of-Function Related Hyper IgE Syndrome.

Background: Hyper-IgE syndrome (HIES) caused by loss-of-function (LOF) mutations in STAT3 gene (STAT3 LOF HIES) is associated with dental and facial abnormalities in addition to immunological defects. The role of STAT3 in the pathogenesis of the dental/facial features is, however, poorly elucidated.

Objectives: Since mechanism of cellular resorption of mineralized tissues such as bone and teeth are similar, we attempted to study the expression of genes involved in bone homeostasis in STAT3 LOF HIES.

TH17 Cells in STAT3 Related Hyper-IgE Syndrome.

Objectives: To assess the utility of T helper17 (TH17) cell enumeration vis-à-vis National Institutes of Health (NIH) scoring in Hyper IgE syndrome (HIES).

Methods: Clinical phenotypes of Hyper IgE syndrome patients with and without STAT3 mutation were analysed and correlated with absolute eosinophil count, serum IgE levels and TH17 cell numbers in 19 patients with clinically suspected HIES and compared with healthy controls (n = 20).

Results: The difference in serum IgE between patients with and without STAT3 mutation and healthy controls was statistically significant (p < 0.

Hyper-IgE syndrome with a novel STAT3 mutation-a single center study from India.

Background: Hyper IgE syndrome (HIES) is a rare primary immunodeficiency disorder characterized by the triad of elevated IgE and eosinophilia, eczema and recurrent skin and pulmonary infections. Mutation in the STAT3 gene accounts for majority of the autosomal dominant and sporadic forms of HIES.

Objective: To report clinical and molecular analyses of patients with Hyper IgE syndrome from a single tertiary care center in India.

Expression of γH2AX may help in defining a genetically more stable subtype of infiltrating ductal carcinoma of breast.

Background & Objectives: Gamma H2AX, a marker of DNA double stranded breaks (DSB) has been found to be over expressed in various tumours. The objective of the present work was to study the expression of γH2AX in infiltrating ductal carcinoma (IDC) and fibroadenoma (FA) cases and to associate the expression in IDC with cytomorphological features and DNA ploidy.

Methods: The expression of γH2AX was studied in fine needle aspirates of 16 cases of IDC and 15 FA cases.

Spontaneously occurring micronuclei in infiltrating ductal carcinoma of breast: a potential biomarker for aggressive phenotype detection?

Chromosomal instabilities (CIN) manifesting as structural or numerical alterations in the chromosomes are common in malignancies like breast cancer. Assessment of CIN in breast cancer may help to understand its etiopathogenesis. Micronucleus (MN) scoring and aneuploidy have been used to assess the presence of CIN in lymphocytes of various malignancies in the past.