Presentation Type

Poster Presentation

In Person or Zoom Presentation

In-Person

Campus

Daytona Beach

Status

Student

Student Year and Major

Senior, Biochemistry

Presentation Description/Abstract

Alopecia areata (AA) is an autoimmune disorder characterized by non-scarring hair loss resulting from T-cell–driven destruction of hair follicles. Central to this process is the dysregulation of Janus kinase 3 (JAK3), a non-receptor tyrosine kinase selectively expressed in hematopoietic cells that mediates γc cytokine receptor signaling. Aberrant JAK3 activity disrupts follicular immune privilege and amplifies pro-inflammatory cytokine cascades, sustaining a chronic autoimmune state. While genetic susceptibility contributes to JAK3 overactivation, converging evidence highlights a pivotal role for environmental exposures in modulating its expression and signaling dynamics. In this framework, we focus on urban air pollutants like particularly fine particulate matter, diesel exhaust constituents, and ozone as key modifiers of JAK3 regulation. These exposures promote oxidative stress, aryl hydrocarbon receptor (AhR), and epigenetic alterations that sensitize γc pathways, collectively priming heightened JAK3–STAT signaling in perifollicular immune cells. Complementary influences from heavy metals and endocrine-disrupting chemicals, as well as conditioning factors such as nutritional status and gut microbiome imbalance, may further skew cytokine homeostasis and lower the threshold for JAK3-dependent autoimmune activation. This work integrates a conceptual, multiscale model of JAK3 activation with structural inspection to illustrate how air pollutants interface with intracellular signaling networks to erode immune privilege and intensify follicular inflammation. Rather than reporting new experiments, we synthesize current data to map plausible exposure-to-signaling routes, identify putative regulatory nodes (redox-sensitive phosphatases, AhR-driven chromatin states, γc receptor trafficking), and outline exposure-responsive biomarkers relevant to AA risk and activity.

Keywords

JAK3, Alopecia Areata, autoimmune, cytokine

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Environmental Modulation of JAK3-Mediated Immune Dysregulation in Alopecia Areata

Alopecia areata (AA) is an autoimmune disorder characterized by non-scarring hair loss resulting from T-cell–driven destruction of hair follicles. Central to this process is the dysregulation of Janus kinase 3 (JAK3), a non-receptor tyrosine kinase selectively expressed in hematopoietic cells that mediates γc cytokine receptor signaling. Aberrant JAK3 activity disrupts follicular immune privilege and amplifies pro-inflammatory cytokine cascades, sustaining a chronic autoimmune state. While genetic susceptibility contributes to JAK3 overactivation, converging evidence highlights a pivotal role for environmental exposures in modulating its expression and signaling dynamics. In this framework, we focus on urban air pollutants like particularly fine particulate matter, diesel exhaust constituents, and ozone as key modifiers of JAK3 regulation. These exposures promote oxidative stress, aryl hydrocarbon receptor (AhR), and epigenetic alterations that sensitize γc pathways, collectively priming heightened JAK3–STAT signaling in perifollicular immune cells. Complementary influences from heavy metals and endocrine-disrupting chemicals, as well as conditioning factors such as nutritional status and gut microbiome imbalance, may further skew cytokine homeostasis and lower the threshold for JAK3-dependent autoimmune activation. This work integrates a conceptual, multiscale model of JAK3 activation with structural inspection to illustrate how air pollutants interface with intracellular signaling networks to erode immune privilege and intensify follicular inflammation. Rather than reporting new experiments, we synthesize current data to map plausible exposure-to-signaling routes, identify putative regulatory nodes (redox-sensitive phosphatases, AhR-driven chromatin states, γc receptor trafficking), and outline exposure-responsive biomarkers relevant to AA risk and activity.

 

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