Synopsis: The ovarian cancer microenvironment induces suppressor neutrophils that inhibit T-cell signaling and metabolic functions. Acquisition of the suppressor phenotype is dependent on several pathways including complement signaling, which can be targeted therapeutically to enhance antitumor immunity.

Sjögren syndrome (SS) is an immunologically complex, chronic autoimmune disease targeting lacrimal and salivary glands. Nonobese diabetic (NOD) mice spontaneously develop inflammation of lacrimal and salivary glands with histopathological features similar to SS in humans including focal lymphocytic infiltrates in the affected glands. The innate immune signals driving lymphocytic infiltration of these glands are not well-defined. Here we evaluate the role of Toll-like receptor (TLR) 7 in the development of SS-like manifestations in NOD mice. We created a Tlr7 knockout NOD mouse strain and performed histological and gene expression studies to characterize the effects of TLR7 on autoimmunity development. TLR7 was required for male-specific lacrimal gland inflammation but not for female-specific salivary gland inflammation. Moreover, TLR7 was required for type 1 diabetes development in male but not female NOD mice. RNA sequencing demonstrated that TLR7 was associated with a type I interferon (IFN) response and a type I IFN-independent B cell response in the lacrimal glands. Together these studies identify a previously unappreciated pathogenic role for TLR7 in lacrimal gland autoimmunity and T1D development in male NOD mice adding to the growing body of evidence supporting sex differences in mechanisms of autoimmune disease in NOD mice.

<p>Supplementary Figure S4: Structure, binding affinity and in vitro potency of FB inhibitor.</p>

<p>Supplementary Figure S1: Gating strategies for flow cytometry and Image-stream.</p>

<p>Supplementary Figure S2: OC ascites fluid exposure increases neutrophil lifespan, increases the proportion of low-density neutrophils, increases LOX-1 expression, and induces neutrophil nuclear hypersegmentation</p>