Abstract

Inhibitory immune receptors are critical for maintaining immune homeostasis; they modulate host response to infection while limiting autoimmunity and immunopathology. Two members of this group, leukocyte-associated immunoglobulin-like receptors 1 and 2 (LAIR1 and LAIR2), are elevated in Cutaneous T-cell Lymphoma (CTCL) patients susceptible to S. aureus infection. We therefore predicted that expression of these receptors would be altered in response to inflammatory stimuli. We found that LAIR1 is regulated in contrasting ways in human and mouse: in humans, LAIR1 increases with LPS and decreases with IFNg, while in mouse, LAIR1 increases with IFNg and decreases with LPS. We additionally used luciferase reporter assays and novel integrative bioinformatics techniques to identify candidate regulatory elements and distinct sets of transcription factors involved in regulation of human and mouse LAIR1 and LAIR2. The expression changes we observed in LAIR1 in response to inflammatory stimuli associated with bacterial infection led us to hypothesize that LAIR1 would play a critical role in the host immune response to S. aureus infection. Therefore, we tested loss of LAIR1 in mice in two infection models: skin and soft tissue infection and pneumonia. In both models, we observed markers of heightened inflammation and neutrophil recruitment as well as phenotypes specific to each tissue environment. In skin, heightened neutrophil and macrophage responses associated with LAIR1 loss resulted in formation of much larger abscesses and inflammatory tissue damage, while in highly vascularized lung, an increase in recruited neutrophils and platelets aided survival in an early infection response. We additionally identified similarities in cytokine responses between LAIR1 loss and CTCL skin lesions that may link our findings in mice to immune defects observed in CTCL. Together, these data demonstrate a novel role for LAIR1 in bacterial infection and represent an opportunity for therapeutic intervention in CTCL.

Committee Chair

Jacqueline Payton

Committee Members

Brian Edelson; Carey-Ann Burnham; Deborah Veis; John Edwards; Peggy Kendall

Degree

Doctor of Philosophy (PhD)

Author's Department

Biology & Biomedical Sciences (Molecular Genetics & Genomics)

Author's School

Graduate School of Arts and Sciences

Document Type

Dissertation

Date of Award

4-15-2026

Language

English (en)

Author's ORCID

https://orcid.org/0000-0002-9600-588X

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Available for download on Thursday, April 13, 2028

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