Up regulation of TYRO3 tyrosine kinase receptor and PROS1 in the myeloid compartment of patients with Langerhans cell Histiocytosis (LCH)

NOWAK W; OLEXEN CM; CASTELLANOS COLLAZO O; TESSONE L; ORTIZ WILCZYÑSKI JM; ESTECHO IG; ERRASTI AE; ROSSO DA; CARRERA SILVA EA

Cancún

Congreso; XII Congress of the Latin American Association of Immunology ? ALAI and XXIII Congress of the Mexican Society of Immunology (SMI).; 2018

ALAI-SMI

<!-- /* Font Definitions */@font-face{font-family:Arial;panose-1:2 11 6 4 2 2 2 2 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536859905 -1073711037 9 0 511 0;}@font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;} /* Style Definitions */p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0in;margin-bottom:.0001pt;mso-pagination:widow-orphan;font-size:11.0pt;font-family:Arial;mso-fareast-font-family:"Times New Roman";mso-ansi-language:ES;mso-fareast-language:ES;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-size:10.0pt;mso-ansi-font-size:10.0pt;mso-bidi-font-size:10.0pt;}@page WordSection1{size:8.5in 11.0in;margin:1.0in 1.25in 1.0in 1.25in;mso-header-margin:.5in;mso-footer-margin:.5in;mso-paper-source:0;}div.WordSection1{page:WordSection1;}--><!-- /* Font Definitions */@font-face{font-family:Arial;panose-1:2 11 6 4 2 2 2 2 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536859905 -1073711037 9 0 511 0;}@font-face{font-family:Arial;panose-1:2 11 6 4 2 2 2 2 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536859905 -1073711037 9 0 511 0;}@font-face{font-family:Cambria;panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536870145 1073743103 0 0 415 0;} /* Style Definitions */p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;line-height:115%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:Cambria;mso-ascii-font-family:Cambria;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Cambria;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Cambria;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES-AR;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-family:Cambria;mso-ascii-font-family:Cambria;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:"ＭＳ 明朝";mso-fareast-theme-font:minor-fareast;mso-hansi-font-family:Cambria;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES-AR;}@page WordSection1{size:595.0pt 842.0pt;margin:1.0in 1.25in 1.0in 1.25in;mso-header-margin:35.4pt;mso-footer-margin:35.4pt;mso-paper-source:0;}div.WordSection1{page:WordSection1;}-->IntroductionTYRO3, AXL and MERTK (TAM)tyrosine kinase receptors and its cognate agonist Protein S (PROS1) have beenidentified as negative regulators of the immune response as well asnon-classical proto-oncogenes, aberrantly expressed in multiple haematologicaland epithelial malignancies. Langerhans Cell (LC) Histiocytosis (LCH) is adisorder characterized by an abnormal accumulation of CD207+CD1a+ myeloid cellsin almost any tissue. The etiology of this disease is still under scientificdiscussion and it is not clear if LCH results from malignant transformation orunbalanced immune response that leads to the proliferation of pathogenic LC-likecells. Our aim is to explore the role of the TAM axis in the pathogenesis ofpediatric LCH.MethodsWe analyzed the expression ofTAM receptors and PROS1 in peripheral blood mononuclear cells of pediatricpatients with confirmed diagnosis of LCH stratified as unisystem or multisystemwith active disease (AD) or non-active disease (NAD) and adult controls. Theexpression levels of PROS1 and TAM receptors were determined by flow cytometryand expressed as fold increase of mean fluorescence intensity (MFI) compared tothe isotype control.ResultsCirculating total CD11b+fraction was significantly expanded in AD (36.4 ± 3.7 % N=11) vs NAD (18.9 ±1.7 % N=12) and adult controls (24.9 ± 1.3 % N=12). Interestingly, thisfraction that is considered the main source of inflammatory myeloid cells,showed higher levels of PROS1 in AD (14.2-fold N=4) compared with NAD (6-foldN=5) and adult controls (6.7-fold N=6). TYRO3 was also up regulated incirculating CD11b+ cells in AD (10.6-fold N=8) compared with NAD (5-fold N=9)and adult controls (4.5-fold N=6).ConclusionsOur results show that higherlevels of TYRO3 and PROS1 are associated with active and multisystem LCHsuggesting that this axis could be involved in the expansion of precursor andpathological LC-like cells.