Activation of c-Kit in dendritic cells regulates T helper cell differentiation and allergic asthma

Abstract

Dendritic cells (DCs) are integral to differentiation of T helper cells into Th1, Th2 and Th17

Exacerbated experimental autoimmune encephalomyelitis in mast-cell-deficient KitW-sh/W-sh mice

“…Intravenous or intracranial injection of BMMCs has been recently found to restore the pool of meningeal MCs in Kit W/W-v mice, leading to the recovery of a WT-like disease course and to the rescue of neutrophil infiltration in the CNS. 20 In our system, although detecting scattered MCs in Kit þ / þ mice in the context of the reticulum formed by the arachnoid, the subdural neurothelium, and the dura mater, in line with previous observations, 29 we could not find MCs populating the [45][46][47] in Kit W-sh/W-sh mice, without finding any difference, according to previous data. 29 However, we cannot exclude that DC-expressed c-Kit has some role on immunization, as demonstrated in a model of allergic asthma, in which Ag/adjuvant exposure induced on DCs the expression of both c-Kit and its ligand, promoting Th2 and Th17 responses.…”

“…Beside MCs, other cells of the immune system may express c-Kit at variable levels and under different circumstances, 44 such as dendritic cells (DCs). 45 C-Kit pharmacological inhibition fosters a productive cross-talk between DCs and natural killer (NK) cells 46 and promotes the differentiation of a DC subset endowed with cytotoxic ability and IFN-g competence. 47 However, as previously reported, 29 we did not observe any difference between naive Kit W-sh/W-sh and Kit þ / þ mice in NK or DC frequency in the spleen (Supplementary Figure S6).…”

Origin and functional specializations of DC subsets in the lung

“…Under these conditions, lung DC receive proper maturation stimuli and release cytokines and costimulatory molecules that become the most important factors in determining the outcome of the cellular immune response. Many groups [41][42][43] have suggested that lung DC have an intrinsic bias to promote Th2 responses, most likely via production of IL-6, but it remains unclear whether this Th2 susceptibility is linked to a particular cDC subset. Recently however, c-Kit expression identified a Th2-prone subset of lung DC [43].…”

“…Many groups [41][42][43] have suggested that lung DC have an intrinsic bias to promote Th2 responses, most likely via production of IL-6, but it remains unclear whether this Th2 susceptibility is linked to a particular cDC subset. Recently however, c-Kit expression identified a Th2-prone subset of lung DC [43]. In our view, any lung DC can induce CTL responses, and Th1, Th2 or Th17 Th effector responses depending on the type and strength of inciting stimulus, with only minor bias due to lineage or surface markers.…”

“…Several investigators have shown that lung DC [9,43,54] or GM-CSF-cultured bonemarrow derived DC injected into the lung [55] are able to induce the typical Th2 response to inhaled allergen. Adoptive transfer studies showed that it is mainly the SIRPa 1 CD11b 1 lung DC that are efficient at Th2 priming, whereas Flt3L-cultured cDC are not [6,8].…”