IL-27 Derived From Macrophages Facilitates IL-15 Production and T Cell Maintenance Following Allergic Hypersensitivity Responses

Abstract

Crosstalk between T cells, dendritic cells, and macrophages in temporal leukocyte clusters within barrier tissues provides a new concept for T cell activation in the skin. Activated T cells from these leukocyte clusters play critical roles in the efferent phase of allergic contact hypersensitivity (CHS). However, the cytokines driving maintenance and survival of pathogenic T cells during and following CHS remain mostly unknown. Upon epicutaneous allergen challenge, we here report that macrophages produce IL-27 which then induces IL-15 production from epidermal keratinocytes and dermal myeloid cells within leukocyte clusters. In agreement with the known role of IL-15 as a T cell survival factor and growth cytokine, this signaling axis enhances BCL2 and survival of skin T cells. Genetic depletion or pharmacological blockade of IL-27 in CHS mice leads to abrogated epidermal IL-15 production resulting in a decrease in BCL2 expression in T cells and a decline in dermal CD8+ T cells and T cell cluster numbers. These findings suggest that the IL-27 pathway is an important cytokine for regulating cutaneous T cell immunity.

Captopril Combined with Furosemide or Hydrochlorothiazide Affects Macrophage Functions in Mouse Contact Hypersensitivity Response

“…Furthermore, we observed the significant reduction in late-phase CHS ear swelling in mice treated with all tested drug combinations ( Figure 2 ). The CHS late phase is mediated by hapten-specific effector T cells and cytotoxic macrophages [ 44 , 45 ], and our findings suggest that these cell activities are diminished by captopril and diuretics, which, together with the reduced CHS early phase, leads to the suppression of CHS response.…”

“…The latter could be detrimental in the case of delayed-type hypersensitivity to non-pathogenic antigens (including self-antigens in autoimmunity), and to contact allergens (haptens). Mouse contact hypersensitivity (CHS) reaction induced by trinitrophenyl (picryl chloride) hapten provides a model of Th1 cell- and macrophage-mediated response for studying these cellular interactions in vivo [ 44 ].…”

Potential of Interleukin (IL)-12 Group as Antivirals: Severe Viral Disease Prevention and Management

“…The receptor is found abundantly on the majority of cell types [ 55 ]. Immune cells such as B cells and macrophages are known to produce IL-27 [ 56 , 57 ]. IL-27 has shown promising antiviral potential due to its pro-inflammatory and anti-inflammatory properties.…”

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines update - III - Cow's milk allergens and mechanisms triggering immune activation

“…Their survival may be fostered by macrophage-derived IL-27, which leads to IL-15 production from keratinocytes, an essential survival factor for T-cells. 116 Contact dermatitis may occur upon skin exposure to milk proteins such as in occupational settings, often when the skin barrier is also impaired due to physical, mechanical or chemical stress. 117…”