Th22 cells are expanded in multiple sclerosis and are resistant to IFN-β

Abstract

Th1 and Th17 cells have been considered as effectors in mouse EAE and in the human counterpart, MS. Recently, IL-22, a Th17-related, proinflammatory cytokine, has been associated with a new Th cell subset, defined as Th22, involved in chronic inflammatory conditions, such as psoriasis; the role of IL-22 in MS has not yet been elucidated. Here, we report that similar to Th17 cells, the number of Th22 cells increased in the PB and the CSF of RR MS patients, especially during the active phases of the disease. However, as opposed to Th17 cells, the expansion of Th22 cells occurred before the active phases of the disease. Th22 cells were found to be specific for the autoantigen MBP and also expressed high levels of CCR6 and T-bet, as for Th17 cells, indicating that Th22 self-reactive cells could have CNS-homing properties and be pathogenic in active RRMS patients. Conversely to Th17 cells, Th22 cells displayed lower levels of IFNAR1 and were insensitive to IFN-β inhibition. These data suggest that expansion of Th22 cells in MS could be one of the factors that critically influence resistance to IFN-β therapy.

TLR2 Stimulation Regulates the Balance between Regulatory T Cell and Th17 Function: A Novel Mechanism of Reduced Regulatory T Cell Function in Multiple Sclerosis

“…Our finding that, similar to observations in the mouse (53), TLR2 activation can promote human Th17 differentiation suggests that peripheral activation of T cells in the presence of microbial TLR1/2 stimuli could drive them to a Th17 phenotype and function. IL-22 has been associated with Th22, a Th subset that is expanded in MS and can react to the myelin autoantigen MBP (54). Th22 cells expressed lower levels of IFNAR1 and were insensitive to IFN-b inhibition, suggesting that expansion of Th22 cells in MS could influence resistance to IFN-b therapy (54).…”

“…IL-22 has been associated with Th22, a Th subset that is expanded in MS and can react to the myelin autoantigen MBP (54). Th22 cells expressed lower levels of IFNAR1 and were insensitive to IFN-b inhibition, suggesting that expansion of Th22 cells in MS could influence resistance to IFN-b therapy (54). Because naturally occurring Tregs express higher levels of TLR2 and TLR1 (10,14,24,55), our data indicate that they may preferentially respond to microbial stimuli in vivo by switching to a Th17/Th22 phenotype and function.…”

T helper 9 cells induced by plasmacytoid dendritic cells regulate interleukin-17 in multiple sclerosis

“…The presence of Th22 cells in MS has also been previously described [15,16], whereas the differentiation and the role of Th9 cells in the disease have never been investigated.…”

Interleukin‐17‐ and interleukin‐22‐secreting myelin‐specific CD4+ T cells resistant to corticoids are related with active brain lesions in multiple sclerosis patients

“…These cells, like Th17, express elevated levels of CCR6, which is required for their migration into the CNS. 14,15 Despite these findings, little is known about the T-cell behaviour in MS patients during the early stages, mainly during the remission phase, and its relation to clinical and radiological activity. It was pointed out that disease activity in the first 2 years after diagnosis may have a prognostic value.…”

“…12 However, production of IL-22 may occur in a unique subset of CD4 + T cells, named Th22, regardless of IL-17 release. 13 Study by Rolla et al 14 has demonstrated a high frequency of myelin-specific Th22 cells in MS patients, especially during the active phases of the disease. These cells, like Th17, express elevated levels of CCR6, which is required for their migration into the CNS.…”