Laboratory of Allergic Diseases

Program Description

The Allergic Inflammation Unit (AIU) is a basic, translational, and clinical lab focused on understanding the immunology of atopic disease through patients with genetic diseases associated with atopic manifestations, patients with immune deficiency and atopy, and patients with severe atopic dermatitis. Through studies of patients and mouse models, we hope to gain better insights into the mechanisms of immunodysregulation that lead to atopic inflammatory disease.

Josh Milner and an NIAID research team have found that wet wrap therapy combined with education on long-term skin care can dramatically improve the lives of children with severe eczema.

Investigation of defects in T-cell receptor signaling and repertoires

Weak T-cell receptor (TCR)-mediated signaling of yet-undifferentiated naïve T cells can lead to inappropriate Th2 differentiation in mouse models. Insufficient TCR diversity can lead to impaired regulation of T cells by other T cells due to insufficient TCR specificity overlap of effector and regulatory populations or due to the absence of competition between T cells leading to the inappropriate emergence of weakly signaling TCRs specific for a given antigen. Our lab is developing and applying techniques to determine whether certain human disorders of atopy may be caused by defects in TCR diversity or signaling function.

Analysis of patients with known genetic diseases associated with atopy

Via the study of selected genetic diseases that have allergic symptoms as an associated manifestation, we hope to derive lessons in the pathophysiology of atopy from the known affected pathways. Examples of diseases studied include the autosomal dominant hyper-immunoglobulin (IgE) syndrome due to mutations in STAT3, Wiskott-Aldrich Syndrome, adenosine deaminase (ADA)-deficiency severe combined immunodeficiency disease (SCID) associated with high IgE and others.

Search for novel genetic diseases associated with atopy

AIU is also centrally focused on defining and understanding new genetic diseases of atopy in order to find novel pathways in the pathogenesis of allergy from these unique diseases. One example is PLCG2-associated antibody deficiency and immune dysregulation (PLAID), which we recently described. Patients with PLAID have cold urticaria, atopy, immune deficiency, and autoimmunity. Research is ongoing into the pathophysiology of PLAID and into the role of the PLCG2 and its pathway in other related disorders.