Abstract
Innate lymphoid cells (ILCs) are classified into distinct subsets termed ILC1, ILC2, and ILC3 cells. The existing literature lacks evidence identifying ILCs and their subsets in the human thymus but already demonstrates that they can exert several functions in regulating immune responses. Furthermore, it was already described that IgG's repertoires could modulate lymphocytes' maturation in the human thymus. Here we aimed to identify ILCs subsets in the human thymus and provide insight into the possible modulatory effect of purified IgG on these cells. Thymic tissues were obtained from 12 infants without an allergic background (non-atopic), and a literature-based peripheral ILCs staining protocol was used. Purified IgG was obtained from non-atopic individuals (n-At), atopic individuals reactive to allergens non-related to dust mites (nr-At), and atopic individuals reactive to the mite Dermatophagoides pteronyssinus (Derp-At). As with all tissues in which they have already been detected, thymic ILCs are rare, but we could detect viable ILCs in all tested tissues, which did not occur with the ILC1 subset. ILC2 and ILC3 NKp44+ subsets could be detected in all evaluated thymus, but ILC3 NKp44- subset could not. Next, we observed that Derp-At IgG could induce the expression of ILC2 phenotype, higher levels of IL-13, and lower levels of IL-4 when compared to IgG purified from non-atopic or non-related atopic (atopic to allergens excluding dust mites) individuals. These results contribute to the elucidation of human thymic ILCs and corroborate emerging evidence about IgG's premature effect on allergy development-related human lymphocytes' modulation.
Highlights
Innate lymphoid cells (ILCs) encompass classic cytotoxic natural killer (NK) cells and lymphoid tissue inducer (LTi), and non-cytotoxic ILC populations [1, 2]
The classification conditions were as follows: (I) non-atopic individuals (n-At): clinically confirmed by medical consultation, without significant IgE-specific titers detected for any tested allergens in an immunoblot assay and without reactivity to any tested allergens in a skin prick test (SPT); (II) atopic non-related to Dermatophagoides Pteronyssinus (Derp) individuals: clinically allergic as confirmed by medical consultation, with clinical symptom-related IgE-specific titers detected for at least two of the non-house dust mite (HDM) tested allergens in an immunoblot assay, and reactivity to at least two of the non-HDM tested allergens in a skin prick test (SPT); (III) Derp atopic individuals (Derp-At): clinically allergic, as confirmed by medical consultation, with clinical symptom-related IgE-specific titers detected for Derp allergen in an immunoblot assay and reactivity to Derp allergen in a skin prick test (SPT)
We applied the gating strategy previously described in the Methods section to 12 health neonatal human thymus, and we could observe that total ILCs could be detected in all tested tissues in frequencies ranging from 0.59 to 6.57% of CD45+LINcells (Figure 1B)
Summary
ILCs encompass classic cytotoxic natural killer (NK) cells and lymphoid tissue inducer (LTi), and non-cytotoxic ILC populations [1, 2]. ILCs can be defined as cell lineage markernegative (Lin−) with a typical lymphoid cell morphology [3,4,5]. ILC3 can distinguish into two subsets based on NKp44 expression [9]. Due to its importance in the murine and human immune system, the development of ILCs had been studied. Given that ILC derives from the common lymphoid progenitor (CLP) and adaptive immune system lymphocytes [25], the detection of these cells in the primary human organ responsible for most adaptive lymphocytes’ maturation has significant importance
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