scholarly journals Therapeutic Implications of Targeting Heat Shock Protein 70 by Immunization or Antibodies in Experimental Skin Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Stefan Tukaj ◽  
Jagoda Mantej ◽  
Michał Sobala ◽  
Katarzyna Potrykus ◽  
Zbigniew Tukaj ◽  
...  

Heat shock proteins (Hsp) are constitutive and stress-induced molecules which have been reported to impact innate and adaptive immune responses. Here, we evaluated the role of Hsp70 as a treatment target in the imiquimod-induced, psoriasis-like skin inflammation mouse model and related in vitro assays. We found that immunization of mice with Hsp70 resulted in decreased clinical and histological disease severity associated with expansion of T cells in favor of regulatory subtypes (CD4+FoxP3+/CD4+CD25+ cells). Similarly, anti-Hsp70 antibody treatment led to lowered disease activity associated with down-regulation of pro-inflammatory Th17 cells. A direct stimulating action of Hsp70 on regulatory T cells and its anti-proliferative effects on keratinocytes were confirmed in cell culture experiments. Our observations suggest that Hsp70 may be a promising therapeutic target in psoriasis and potentially other autoimmune dermatoses.

1999 ◽  
Vol 67 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Jeffrey Kopacz ◽  
Nirbhay Kumar

ABSTRACT γδ T cells accumulate during Plasmodium infections in both murine and human malarias. The biological role of these cells and the antigens that they recognize are not clearly understood, although recent findings indicate that γδ T cells in general influence both innate and antigen-specific adaptive host responses. We examined the accumulation of γδ T cells elicited during infection with virulent and avirulent Plasmodium yoelii parasites in relatively susceptible and resistant strains of mice. Our results indicated that in nonlethal malaria infections, γδ T cells comprise a larger proportion of splenic T cells than in lethal infections and that only a live infection is capable of inducing an increase in the percentage of γδ T cells in vivo. Furthermore, we demonstrate that γδ T cells elicited during a P. yoelii infection respond by proliferation in vitro to P. falciparum heat shock proteins (HSPs) of 60 and 70 kDa, suggesting a possible immunological involvement of parasite HSPs in this arm of the cellular immune response during malarial infection in mice.


1999 ◽  
Vol 276 (3) ◽  
pp. L501-L505
Author(s):  
Claudia Racine ◽  
Evelyne Israël-Assayag ◽  
Yvon Cormier

The current study was done to look at a possible role of heat shock proteins (HSPs) in hypersensitivity pneumonitis (HP). The specific aims were to determine whether there was a difference in the expression of HSP72 in alveolar macrophages (AMs) between mice challenged with HP antigen and saline-treated control mice and between AMs obtained by bronchoalveolar lavage from 18 patients with HP and 11 normal subjects. The expression of HSP72 was studied under basal conditions and under a mild heat shock. HSP72 expression by AMs in response to in vitro stimulation with Saccharopolyspora rectivirgula was lower in AMs of control mice than in those of HP animals. HSP72 was constitutively expressed in AMs of both normal and HP subjects. Densitometric ratios showed that AMs from normal subjects responded to heat shock with a 39°C-to-37°C ratio of 1.72 ± 0.18 (mean ± SE), and AMs from HP patients responded with a ratio of 1.16 ± 0.16 ( P = 0.0377). This decreased induction by additional stress of AMs could lead to an altered immunoregulatory activity and account for the inflammation seen in HP.


1983 ◽  
Vol 61 (6) ◽  
pp. 456-461 ◽  
Author(s):  
M. Ropp ◽  
A. M. Courgeon ◽  
R. Calvayrac ◽  
M. Best-Belpomme

In vitro cultured Drosophila melanogaster cells were shown to be aerobic and several kinetic parameters of their respiration were measured. This allowed us to define experimental conditions for a transient period of anaerobiosis followed by a reexposure to normal oxygenation. This treatment, applied without any change of temperature, induced not only the heat-shock proteins, but also a new specific peptide of 27 000 daltons and a twofold increase of the maximal rate of O2 uptake. This evokes a common molecular mechanism activated either by heat or by O2, which could involve the increase of the products of oxygen reduction such as the superoxide ion.


2014 ◽  
Vol 21 (6) ◽  
pp. 564-571 ◽  
Author(s):  
Sourav Roy ◽  
Monobesh Patra ◽  
Suman Nandy ◽  
Milon Banik ◽  
Rakhi Dasgupta ◽  
...  

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Stephan Hailfinger ◽  
Klaus Schulze-Osthoff

Abstract Psoriasis is a frequent autoimmune-related skin disease, which involves various cell types such as T cells, keratinocytes and dendritic cells. Genetic variations, such as mutations of CARD14, can promote the development of the disease. CARD14 mutations as well as the stimulation of immune and cytokine receptors activate the paracaspase MALT1, a potent activator of the transcription factors NF-κB and AP-1. The disease-promoting role of MALT1 for psoriasis is mediated by both its protease activity as well as its molecular scaffold function. Here, we review the importance of MALT1-mediated signaling and its therapeutic implications in psoriasis.


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