New insights into basophil biology: initiators, regulators, and effectors of type 2 inflammation

Abstract

Recent studies indicate that basophils perform essential functions in multiple models of Th2 cytokine-dependent immunity and inflammation. In addition to their role as late phase effector cells, basophil populations can express MHC class II and costimulatory molecules, migrate into draining lymph nodes, present antigen to naive CD4(+) T cells, and promote Th2 cell differentiation. In this context, basophils have been shown to contribute to the induction and propagation of Th2 cytokine responses following exposure to some helminth parasites or allergens. In this review, we discuss recent studies that provide new insights into basophil development, regulation, and effector function. In addition, we discuss the ability of basophils to act both independently and cooperatively with dendritic cells to support Th2 cytokine-mediated inflammation.

Figure 1. Basophil development, activation and function

Basophils develop from precursor cells in the BM that expand in number in response to growth factors including IL-3 (➀ and ➁). Once mature, basophils exit the BM and enter the periphery (➂). Mature basophils can be activated by an array of signals including those mediated by cytokines (IL-3, IL-33 and IL-18), antibodies (IgG, IgD and IgE) and antigens (➃). Although the tissue-restricted signals that regulate basophil effector function are poorly characterized, activated basophils are known to produce histamines (➄), cytokines (➅) and chemokines (➆). Some basophil populations migrate to draining LNs (➇) while others accumulate in inflamed tissues during an ongoing inflammatory response (➈).

Figure 2. Basophil- and dendritic cell-specific contributions to Th2 cytokine responses

Summary of experiments in which mice were challenged with papain, papain + ovalbumin (OVA), house dust mite (HDM), primary infection with Nippostrongulys brasiliensis (Nippo 1°), secondary infection with N. brasiliensis (Nippo 2°), Trichuris muris, Schistosoma mansoni (Schisto), or S. mansoni eggs (Schisto egg). Basophil populations were modified by treatment with anti-FcεRIMAR-1), expression of Cre recombinase under the mast cell protease 8 (Mcpt8Cre), or treatment with anti-CD200R3 (Ba103). Dendritic cell populations were modified by delivery of diptheria toxin to mice that express the diptheria toxin receptor under the CD11c promoter (CD11c-DTR), DC ablated mice (DeltaDC), or treatment with MAR-1. Th2 cytokine responses were evaluated post-basophil or DC manipulation. Experiments that did not test (NT) the contributions of basophils or DCs on Th2 cytokine response are indicated.