BAFF promotes heightened BCR responsiveness and manifestations of chronic GVHD after allogeneic stem cell transplantation.

Patients with chronic graft-versus-host disease (cGVHD) have increased B cell-activating factor (BAFF) levels, but whether BAFF promotes disease after allogeneic bone marrow transplantation (allo-BMT) remains unknown. In a major histocompatibility complex-mismatched model with cGVHD-like manifestations, we first examined B-lymphopenic μMT allo-BMT recipients and found that increased BAFF levels in cGVHD mice were not merely a reflection of B-cell number. Mice that later developed cGVHD had significantly increased numbers of recipient fibroblastic reticular cells with higher BAFF transcript levels.

Fate Mapping In Vivo to Distinguish Bona Fide Microglia Versus Recruited Monocyte-Derived Macrophages in Retinal Disease.

With the new understanding that adult microglia in mice have embryonic origins and are maintained in situ throughout life, it has become pertinent to now understand how these unique cells differ from monocyte-derived macrophages. The latter are recruited into the neural retina (and elsewhere in CNS) in certain diseased states, such as in various forms of retinal degeneration. However, phenotypic markers expressed by microglia and monocyte-derived macrophages largely overlap, thereby making it technically challenging to distinguish the two cell types in disease.

SYK inhibitor entospletinib prevents ocular and skin GVHD in mice.

Graft-versus-host disease (GVHD) is a major complication of hematopoietic stem cell transplantation (HCT). The tyrosine kinase SYK contributes to both acute and chronic GVHD development, making it an attractive target for GVHD prevention. Entospletinib (ENTO) is a second-generation highly selective SYK inhibitor with a high safety profile.

Resolvin D1 treatment on goblet cell mucin and immune responses in the chronic allergic eye disease (AED) model.

Severe, chronic eye allergy is an understudied, vision-threatening condition. Treatments remain limited. We used a mouse model of severe allergic eye disease (AED) to determine whether topical application of the pro-resolution mediator Resolvin D1 (RvD1) terminates the response.

Neutrophils cause obstruction of eyelid sebaceous glands in inflammatory eye disease in mice.

Meibomian glands (MGs) are sebaceous glands of the eyelid margin that secrete lipids needed to avert tear evaporation and to help maintain ocular surface homeostasis. Obstruction of MGs or other forms of MG dysfunction can promote chronic diseases of the ocular surface. Although chronic eyelid inflammation, such as allergic eye disease, is an associated risk factor for obstructive MG dysfunction, it is not clear whether inflammatory processes contribute to the pathophysiology of MG obstruction.

Induction and Characterization of the Allergic Eye Disease Mouse Model.

Ocular IgE-associated allergy ranges from mild disease (seasonal and perennial allergic conjunctivitis) to more chronic/severe and vision-threatening forms (atopic and vernal keratoconjunctivitis). Whereas mild forms of disease have been studied extensively, less is known about the more chronic forms. Our lab has helped to address this knowledge gap by developing and characterizing an allergen-induced, chronic/severe, IgE-associated model of ocular allergy referred to as the severe allergic eye disease (AED) model.

A Commencement for Eye Commensals.

"Paucibacterial" levels of the normal eye surface have left immunologists wondering whether a true microbiome exists there. In this issue of Immunity, St. Leger et al.

New insights into mononuclear phagocyte biology from the visual system.

Major advances in mononuclear phagocyte biology have been made but key questions pertinent to their roles in health and disease remain, including in the visual system. One problem concerns how dendritic cells can trigger immune responses from certain tightly regulated immune- privileged sites of the eye. Another, albeit separate, problem involves whether there are functional specializations for microglia versus monocytes in retinal neurodegeneration.

Classical dendritic cells mediate fibrosis directly via the retinoic acid pathway in severe eye allergy.

Fibrosis is a shared end-stage pathway to lung, liver, and heart failure. In the ocular mucosa (conjunctiva), fibrosis leads to blindness in trachoma, pemphigoid, and allergy. The indirect fibrogenic role of DCs via T cell activation and inflammatory cell recruitment is well documented.

Involvement of corneal lymphangiogenesis in a mouse model of allergic eye disease.

Purpose: The contribution of lymphangiogenesis (LA) to allergy has received considerable attention and therapeutic inhibition of this process via targeting VEGF has been considered. Likewise, certain inflammatory settings affecting the ocular mucosa can trigger pathogenic LA in the naturally avascular cornea. Chronic inflammation in allergic eye disease (AED) impacts the conjunctiva and cornea, leading to sight threatening conditions.

T helper subsets in allergic eye disease.

Purpose Of Review: Ocular allergy is an IgE-mediated disease that results in inflammation of the conjunctiva and, in more severe cases, the cornea. This is driven by an immediate hypersensitivity response via mast cells, followed by a late phase response mediated by eosinophils both of which are indeed dependent on T helper (Th) lymphocyte activity. Here, we provide an update on Th subsets [Th1, Th2, Th17, and T regulatory (Treg)] and their relevance in ocular allergy.

Ocular mucosal CD11b+ and CD103+ mouse dendritic cells under normal conditions and in allergic immune responses.

Steady state dendritic cells (DC) found in non-lymphoid tissue sites under normal physiologic conditions play a pivotal role in triggering T cell responses upon immune provocation. CD11b+ and CD103+ DC have received considerable attention in this regard. However, still unknown is whether such CD11b+ and CD103+ DC even exist in the ocular mucosa, and if so, what functions they have in shaping immune responses.

New twists to an old story: novel concepts in the pathogenesis of allergic eye disease.

The prevalence of allergy is rising globally at a very significant rate, which is currently at 20-40% of individuals in westernized nations. In the eye, allergic conditions can take on the acute form such as in seasonal and perennial allergic conjunctivitis, or a more severe and debilitating chronic form such as in vernal and atopic keratoconjunctivitis. Indeed, some key aspects of allergic eye disease pathophysiology are understood, such as the role of mast cells in the acute allergic reaction, and the contribution of eosinophils in late-onset and chronic allergy.

γδ T cells are required for maximal expression of allergic conjunctivitis.

Purpose: To determine the function of γδ T cells in early- and late-phase responses in allergic conjunctivitis.

Methods: Wild-type (WT) C57BL/6 and γδ T cell-deficient (TCR-δ(-/-)) mice were immunized intraperitoneally and challenged topically for 7 consecutive days with short ragweed pollen. Natural killer T (NKT) and γδ T cell-double-deficient mice were generated by treating TCR-δ(-/-) mice with anti-CD1d antibody.

NKT cells are necessary for maximal expression of allergic conjunctivitis.

Allergic conjunctivitis (AC) is elicited by immediate hypersensitivity responses to environmental agents. It is initiated by a T(h)2-dominated immune response that is characterized by production of IgE antibodies and eosinophilic infiltration. By using an experimental mouse model of AC induced by short ragweed (SRW) pollen, we show that sensitized Jalpha18(-/-) mice, which lack type I NKT cells, and CD1d(-/-) mice, which lack type I and type II NKT cells, exhibited a decrease in tearing, lid edema, conjunctival edema and vasodilatation and eosinophil infiltration into the conjunctiva when compared with wild-type (WT) mice in both T(h)1- and T(h)2-prone hosts (C57BL/6 and BALB/c mice, respectively).